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 clone a new nuclear receptor, we screened a rabbit heart complementary DNA (cDNA) library with degenerate oligonucleotide probes corresponding to the DNA-binding domain of nuclear receptors, which is highly conserved among receptors. One of the cDNA clones, clone 23, encodes a novel protein of 596 amino acids, and predicted molecular mass is 66 kDa. Homology search analysis identified this protein as rabbit TR4 (TR4-0). We also cloned the cDNA encoding a rabbit TR4 isoform (TR4-1), which lacks the putative C-terminal ligand-binding domain (350 amino acids) caused by a 23-bp exon deletion, which probably occurred during messenger RNA (mRNA) splicing. Northern blot analysis showed that TR4s are expressed with two kinds of mRNAs (9.0 kb and 2.8 kb), both of which are relatively abundant in brain, testis, and bone. RT-PCR analysis, using pairs of primers specific for each TR4, showed that both types of receptor express in various tissues. Furthermore, both are present in primary osteoblasts and bone marrow cells, though the mRNA levels of TR4-0 were much higher than those of TR4-1. A functional study, using a transient transfection assay, showed that both receptors suppressed retinoid X receptor (RXR)-retinoid acid receptor, RXR-TR, and RXR-VDR-mediated transactivation significantly in COS-1 and osteosarcoma cells (UMR-106, ROS17/2.8) and that TR4-0 was much more effective than TR4-1. Unexpectedly, we found that the TR4s effectively suppressed estrogen receptor-mediated transactivation in bone cells, but neither in kidney (COS-1) nor breast cancer cells (MCF-7, one of the major target cells of the estrogen action). Thus, the present study shows a novel property of the TR4 orphan receptor, acting as a bone cell-specific repressor in the estrogen receptor-mediated signaling pathway.
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PMID:Cloning of rabbit TR4 and its bone cell-specific activity to suppress estrogen receptor-mediated transactivation. 942 16

A quantitative method for measuring 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was developed utilizing a luciferase reporter gene under the control of the highly inducible 25-hydroxyvitamin D3 24-hydroxylase promoter in a stably transfected cell line. Transient transfections with constructs containing the 24-hydroxylase gene promoter 5' to a luciferase reporter were first performed in cell lines with high levels of vitamin D receptor, i.e., the rat osteosarcoma (ROS 17/2.8) and human breast cancer (T-47D) cell lines. ROS 17/2.8 cells, stably transfected with the plasmid, gave a 60-fold stimulation with 10(-10) M 1,25-(OH)2D3. A standard curve was constructed showing a large range of response to 1,25-(OH)2D3 (1 pg to 1 ng). The assay was adapted to microtiter plates, which permits a large number of samples to be assayed simultaneously. Other metabolites of vitamin D and analogs such as 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and 1 alpha-hydroxyvitamin D3 have negligible effects on the detection of 1,25-(OH)2D3, thus eliminating the need for purification of sample. The sensitivity of the method permitted the use of 100 microliters of serum with excellent results. Comparison of this method with a commercially available assay demonstrates that it gives higher sensitivity, simpler manipulations, and comparable results.
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PMID:A highly sensitive method for large-scale measurements of 1,25-dihydroxyvitamin D. 944 54

Melatonin was previously shown to inhibit proliferation of MCF-7 human breast cancer cells. In this study the effect of melatonin on MCF-7 cells was further examined, while human cervical carcinoma (HeLa), osteosarcoma (MG-63) and lymphoblastoid (TK6) cells were tested for the first time. Haemocytometer counts, DNA content, flow cytometry and indirect immunofluorescence for nucleolar proteins, actin and beta-tubulin showed no differences in the growth, cell cycle or morphology between melatonin-exposed and control cells. The direct antiproliferative effect of melatonin thus seems to be confined to a melatonin-responsive subclone of MCF-7 cells and not applicable to the majority of cancer cells.
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PMID:Melatonin has no effect on the growth, morphology or cell cycle of human breast cancer (MCF-7), cervical cancer (HeLa), osteosarcoma (MG-63) or lymphoblastoid (TK6) cells. 946 86

The expression of Bfl-1 gene, a novel Bcl-2 related gene, was determined by Northern blot analysis using a radiolabeled cDNA specific for Bfl-1 gene in 82 surgically resected tissue specimens of 28 gastric cancers, 15 colon cancers, nine breast cancers, eight bone and soft tissue sarcomas, five ovarian cancers, nine colon adenomas and eight gastric adenomas. A high rate of expression was observed in gastric and colon cancer, at 86 and 93%, respectively. In breast cancer, bone and soft tissue sarcoma and ovarian cancer, the expression rate was 33, 25 and 40%, respectively. In stomach cancer, the expression rate of Bfl-1 gene in metastatic lymph nodes was 82%, which was higher than 50% of the primary sites (p < 0.02). The intensity of RNA bands of the gastric cancer specimens was compared according to the stage, demonstrating that there was no difference in the expression levels of Bfl-1 gene between the stages in both primary sites and metastatic lymph nodes. Bfl-1 gene was expressed in three (33%) out of nine adenomas of the colon, while it was not detected in all eight gastric adenomas, We also examined the RNA expression of Bfl-1 gene in 22 human cancer cell lines consisting of five stomach cancer, four squamous cell carcinoma, three lung cancer, three cervical cancer, two colon cancer, two brain cancer, two leukemia and one osteosarcoma cell lines. Bfl-1 gene band was detected in one (5%) cervical cancer cell line, SiHa. The results of cancer tissue specimens indicate that Bfl-1 gene may play an important role in carcinogenesis of human cancers and may be involved in a relatively early phase of the adenoma-carcinoma sequence in colon cancer development. However, the mechanism responsible for the very low rate of expression in established cell lines is not clearly understood and further investigation is necessary to clarify the mechanism involved.
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PMID:Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines. 949 79

The principal cause of death from most forms of cancer is metastatic disease. Cancer cells appear to grow quickly out of the control of the normal host regulatory mechanisms. Many factors contribute to this unrestrained proliferation, including increased metalloproteinase activity causing degradation of the extracellular matrix surrounding cancer cells, angiogenesis permitting easy access of the cells to the bloodstream and decrease or loss of programmed cell death, or apoptosis, an important mechanism for removal of abnormal or senescent cells. Treatment modalities targeted towards arresting cancer cell proliferation and spread are needed to improve the survival of patients with cancer. Vitamin D3, 1,25-dihydroxychole-calciferol D3, has been shown to induce apoptosis in the human breast cancer cell line, MCF-7. We have studied the effects of three concentrations of vitamin D3 on the human breast cancer cell line, MDA-MB-435, the human prostate cancer cell line, LNCaP, and a human osteosarcoma cell line, U20S. We report here that vitamin D3 strikingly inhibits cell proliferation and induces apoptosis in all three cell lines.
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PMID:Effects of vitamin D3 on proliferation of cancer cells in vitro. 957 Mar 87

Second malignancy after childhood neoplasms is a well-known complication. However, frequency differs considerably according to the types of primary neoplasm and the specifics of therapy. Ten patients with a second malignancy after being cured of the primary tumor are described. There were 2 patients with acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma developed osteosarcomas in the irradiation field after a latent period of 7 and 14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor. One patient with acute lymphoblastic leukemia developed a secondary AML 10 years after achieving initial remission, and a meningioma was diagnosed in another patient with cured acute lymphoblastic leukemia. One patient died of peritoneal sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid leukemia. All patients received radiotherapy for the primary neoplasms. Secondary neoplasms in other patients were probably missed because they occurred in adulthood when the patients were transferred to other medical centres. It is impossible to trace these patients because central registration of patients with neoplasms is lacking. It is therefore important to establish a central cancer registry for the whole of Switzerland. Second malignancy after childhood cancer is not a rare event and requires long-term follow-up of patients with neoplasms.
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PMID:[Insufficient understanding of second tumors after childhood neoplasms in Switzerland]. 958 99

Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage previously described most frequently after breast cancer and Hodgkin disease treatment with radio and/or chemotherapy. We report two cases of classical osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive loco-regional irradiation in the second case.
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PMID:[Secondary head and neck osteosarcoma following treatment of undifferentiated nasopharyngeal neoplasms (UCNT)]. 958 63

The physiologically active metabolite of the vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a major regulator of mineral homeostasis. Recent evidence also suggests its role in regulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)2D3 to hyperproliferative disease, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study, the efficacy of the vitamin D2 analog, 1,24(S)-dihydroxyvitamin D2 (1,24(S)-(OH)2D2) in the inhibition of cancer cell proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH)2D3. By the [3H]-thymidine incorporation procedure, 1,24(S)-(OH)2D2 is as equipotent as 1,25(OH)2D3 in inhibiting the proliferation of five different cell lines, ROS 17/2.8, the rat osteosarcoma cell line, MCF-7, the human breast cancer cell line, HD-11, the chick bone marrow v myc transformed cell line, HT-29, the human colon cancer cell line and HL-60, the human leukemia cell line. The inhibitory action was dose and time-dependent. The NBT reduction method indicated that 1,24(S)-(OH)2D2 induces the differentiation of the human leukemia cell (HL-60) to the same extent as 1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and 1,25(OH)2D3 with regard to the above activities, they differ in their effects on calcium regulation. In conclusion, the present results encourage the use of 1,24(S)-(OH)2D2 for the treatment of cancer disease in vivo.
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PMID:The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines. 967 3

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.
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PMID:Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma. 974 49

Pulmonary metastases are the main cause of death of patients with several types of cancer, including osteosarcoma, renal cell carcinoma, malignant melanoma, and breast cancer. Previously, we demonstrated that intralesional injection of the recombinant adenovirus (Ad) vector containing the herpes simplex virus thymidine kinase (TK) gene driven by an osteocalcin (OC) promoter (Ad-OC-TK) effectively suppressed the growth of osteosarcoma cells in vitro and tumors in vivo in a tumor-specific manner when supplemented with the prodrug acyclovir (ACV). In this communication, we studied the potential efficacy of the treatment of osteosarcoma pulmonary metastases with a systemic delivery route of Ad-OC-TK supplemented with ACV. We established osteosarcoma lung metastases in nude mice by the intravenous injection of rat osteosarcoma cells, ROS 17/2.8. These cells colonized and formed tumor nodules within 1 week in the lungs of nude mice. Whereas systemic delivery of a recombinant Ad vector containing the Escherichia coli beta-galactosidase (beta-gal) gene driven by a Rous sarcoma virus universal promoter (Ad-RSV-beta-gal) resulted in the nonspecific expression of beta-gal activity in the lung parenchyma, Ad-OC-beta-gal administration resulted in specific beta-gal expression in tumor cells deposited in the lung. When nude mice bearing ROS 17/2.8 lung tumors were treated with systemic Ad-OC-TK through tail vein administration, subsequent intraperitoneal ACV treatment significantly decreased the number of tumor nodules (P < .0001) and the net lung wet weight (P = .0005) while significantly increasing (.005 < P < .01) the survival of animals, when compared with untreated and Ad-OC-TK- or ACV-treated control groups. These results suggest that Ad-OC-TK/ACV may be used as a systemic therapy for the treatment of osteosarcoma lung metastasis.
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PMID:In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy. 982 46


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