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)

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment. The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P less than 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P less than 0.05) with percentage of necrosis.
Am J Vet Res 1991 Dec
PMID:In vitro assay of nuclear uptake of doxorubicin hydrochloride in osteosarcoma cells of dogs. 178 8

A desirable goal in the treatment of osteogenic sarcoma is preservation of a limb, without sacrificing the principles of cancer surgery. This study describes the author's experience at the Memorial Sloan-Kettering Cancer Center in New York with limb salvage surgery for osteogenic sarcoma. One hundred ninety two patients are included in this study. The study shows that pre-operative chemotherapy is successful as demonstrated by the improved cure rates of each resection group. It was also found that limb sparing surgery is successful with or without chemotherapy as long as the surgical margins are adequate. Pulmonary resection surgery has also been shown to be successful as has surgery for a second bone involvement.
Compr Ther 1991 Dec
PMID:Complicated problems in osteogenic sarcoma including pulmonary metastasis, second bone involvement and cure rates. 179 Jun 60

We recently showed that leukemia inhibitory factor (LIF) stimulates 45Ca release from neonatal mouse calvariae in vitro and that it increases DNA and protein synthesis in this model. To elucidate further the actions of LIF on bone we now report the effects of this cytokine on DNA synthesis and cell proliferation in isolated fetal rat osteoblasts and in the osteogenic sarcoma cell line, UMR-106. In both actively growing and growth-arrested rat osteoblasts, LIF stimulated [3H]thymidine incorporation in a dose-dependent manner. The increase in DNA synthesis was time dependent, was associated with an increase in the number of osteoblasts, and was not blocked by indomethacin. LIF-treated cells showed reduced [3H]thymidine incorporation in comparison with control, as they approached confluence, possibly because of the increased cell density in the LIF-treated cultures. In UMR-106 cells, treatment with LIF inhibited [3H]thymidine incorporation in both actively growing and growth-arrested cultures. The effect was dose dependent and sustained with time. There was a corresponding decrease in cell numbers. It is concluded that although LIF causes an early stimulation of proliferation in isolated osteoblasts, it has opposing effects on UMR-106 cells. It is not possible to determine which of these effects is more relevant to the actions of LIF in vivo. The demonstration of a LIF effect on both these cell types, however, provides further evidence that this cytokine acts directly on osteoblasts.
J Bone Miner Res 1991 Dec
PMID:Regulation of osteoblast proliferation by leukemia inhibitory factor. 179 39

According to the natural development of the bone-marrow-derived osteosarcoma (BMDOS) of long bones, it was classified into 4 stages. Stage A: The tumor is confined within the marrow cavity; stage B: The tumor has perforated the bone cortex; stage C: The tumor has involved the contiguous joint cartilage; and stage D: The tumor has metastasized to the lung. According to this staging, 64 cases of BMDOS of the long bones were investigated and the relationship between staging and prognosis, between different kinds of treatment and prognosis, etc. were analyzed. This staging of BMDOS of long bones proved to be very significant clinically. Only those cases in stage A or B can be expected to survive for 5 years; and because most of the non-survivors die within 2.5 years after treatment, this time is considered a critical period. Tumor involvement of the contiguous joint cartilage is also a critical sign. As to prognosis, the stage of the tumor is a more accurate indicator than is the method of treatment. And finally, the prognosis of patients treated with chemotherapy and amputation was generally better than that of patients treated by amputation alone.
Chin Med Sci J 1991 Dec
PMID:A staging of bone-marrow-derived osteosarcoma of long bones with a 64-case analysis. 181 56

Boron analogues of piperidine, piperazine, morpholine, and imidazole proved to be cytotoxic against the growth of murine and human tissue culture cells. Significant activity was demonstrated for single-cell suspensions of L1210 lymphoid leukemia, Tmolt3 lymphoblastic leukemia, and HeLa-S3 cervical carcinoma. Trimethylamine-imidazole carbonyldihydroborane 17 demonstrated activity against solid tumor growth of human colorectal adenocarcinoma, KB nasopharynx, and osteosarcoma. In addition, 4-methylpiperidine-carbomethoxyborane 12, 2-methylimidazole-3-cyanoborane 16, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were active against the KB nasopharynx growth. Piperidine-cyanoborane 2, piperidine-carboxyborane 4, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were effective in reducing the growth of osteosarcoma cells. The imidazole derivatives 13-19, as well as 4-methylpiperidine-carboxyborane 11 and carbomethoxyborane 12, demonstrated good activity against lung bronchogenic and glioma growth. In the in vivo studies, N-methylmorpholine-carboxyborane 7,4-phenylpiperidine-carboxyborane 9, 4-phenylpiperidine-carbomethoxyborane 10, 4-methylpiperidine-carboxyborane 11, imidazole cyanoborane 14, and 1-methylimidazole-3-carbomethoxyborane 18 demonstrated the best activity against Lewis Lung growth and P388 lymphocytic leukemia growth in mice. Mode of action studies in L1210 leukemia cells demonstrated that piperidine-carboxyborane 4 and N-methylmorpholine-carboxyborane 7 inhibited DNA synthesis, purine synthesis at PRPP amido transferase and IMP dehydrogenase sites, and thymidine kinase and thymidine diphosphate kinase activities, while lowering d(NTP) pool levels. Also, DNA strand scission was evident after incubation with these drugs.
J Pharm Sci 1991 Dec
PMID:Synthesis and antineoplastic activity of some cyano-, carboxy-, carbomethoxy-, and carbamoylborane adducts of heterocyclic amines. 181 71

It is generally thought that the germinal mutation of tumor-suppressor genes predisposes the affected children to the development of certain types of hereditary tumors while the somatic mutation of the same genes links to the development of non-hereditary tumors. Retinoblastoma susceptibility gene (RB gene) is a prototype of such genes. We studied the parental origin of new mutation of the RB gene in the sporadic hereditary and non-hereditary retinoblastoma and osteosarcoma. The results showed a preferential involvement of parental genome in the new germinal as well as initial somatic mutations. The male-directed mutagenesis even in the somatic cells has been implicated as a reflection of germinal origin of mutation, even for non-hereditary tumors as a manifestation of mutational mosaicism associated with delayed mutation. The importance of the new mutations occurring as mosaics should be emphasized in the evaluation of cancer risks from parental exposures to radiation and chemicals.
J Radiat Res 1991 Dec
PMID:Somatic and germinal mutations of tumor-suppressor genes in the development of cancer. 182 63

Recombinant GH and IGF-I/-II were studied for their capacity to directly influence the growth of human bone cells maintained under defined serum-free conditions. Normal human osteoblast-like cell (HOB) cultures were established from trabecular bone explants obtained from adult human femoral head samples. IGF-I and IGF-II as well as GH stimulated the growth of the HOB cultures in a dose-dependent manner. Growth stimulatory effects were also found using the human osteogenic sarcoma cell line, SaOS-2. IGF-I and -II were powerful enhancers of the SaOS-2 cell growth and their effects greatly exceeded GH effects on these cells. The role of endogenously produced IGFs was studied using a specific monoclonal antibody to IGF-I having a partial cross-reactivity with IGF-II (sm1.2B). The IGF-I stimulated HOB growth was completely neutralised by sm1.2B to the level of control+antibody which in general showed a slight stimulation compared to controls without the antibody. Interestingly, sm1.2B was not able to interfere with the action of GH on the HOB suggesting that GH effects may be attributed to an action independent of endogenous IGF-I/-II. Unlike the HOB, SaOS-2 cells were strongly inhibited by sm1.2B in control medium indicating an autocrine role of IGF-I/-II in osteosarcoma cell growth. Sm1.2B completely neutralised the stimulatory effects of IGF-I and IGF-II on the SaOS-2 cells. Moreover, GH effects on the osteogenic sarcoma cells were abolished by the anti-IGF antibody showing that GH was acting via endogenously produced IGFs.(ABSTRACT TRUNCATED AT 250 WORDS)
Growth Regul 1991 Dec
PMID:Effects of recombinant human insulin-like growth factor I and II (IGF-I/-II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cells and human osteogenic sarcoma cells. 184 48

We have previously reported that 1,25(OH)2D3 stimulated the cellular alkaline phosphatase (ALP) activity and increased the steady-state level of ALP mRNA in a human osteosarcoma cell line (TE-85), under serum-free conditions. To define the molecular mechanism by which 1,25(OH)2D3 acts to stimulate ALP activity, the time courses of the increases in ALP activity and in the steady-state ALP mRNA level in response to 1,25(OH)2D3 were evaluated. 1,25(OH)2D3 progressively increased the steady-state level of ALP mRNA from 5 to 24 h of treatment, at which time a plateau was observed. In contrast, no significant increase in ALP-specific activity was detected until after 10 h of treatment, at which time the activity increased linearly with time up to 72 h. These time courses are consistent with the premise that the increased ALP activity was the result of increased gene expression. Nuclear runoff analysis indicated that the transcription rate of the ALP gene was more than five-fold higher in the 1,25(OH)2D3-treated cells than in the control cells. In addition, it was found that 1,25(OH)2D3 treatment increased ALP mRNA stability. The 1,25(OH)2D3-induced increase in ALP mRNA stability was not due to an interaction of the 1,25(OH)2D3-receptor complex with the ALP mRNA, since the removal of 1,25(OH)2D3 did not abolish its stabilizing effect. In the presence of cycloheximide, the stabilizing effect of 1,25(OH)2D3 was abolished, suggesting that a 1,25(OH)2D3-inducible protein factor was involved. Based on these findings, we have proposed a model in which 1,25(OH)2D3 stimulated ALP activity in human bone cells through mechanisms involving both (1) increased transcription of the ALP gene and (2) increased stability of ALP mRNA, an effect which requires the de novo synthesis of a protein, a putative ALP mRNA "stabilizing factor."
Arch Biochem Biophys 1991 Dec
PMID:1,25-Dihydroxyvitamin D3 stimulates both alkaline phosphatase gene transcription and mRNA stability in human bone cells. 195 46

We showed recently that the initial peak cytosolic ionized calcium ([Ca2+]i) response to PTH (2-min exposure) is preserved relative to the cAMP response in osteoblast-like rat osteosarcoma cells (ROS 17/2.8) desensitized by 72-h exposure to PTH. We attempted in the present studies to determine the mechanisms for preservation of the [Ca2+]i response and to explore the effects of longer PTH rechallenges. The [Ca2+]i response to a 20-min perifusion with rat PTH [rPTH-(1-34)] was monitored by aequorin luminescence in both naive and PTH-desensitized ROS 17/2.8 cells. The responses of both naive and desensitized cells consisted of two phases: an initial peak, followed by an intermediate plateau that was sustained in the presence of PTH. We observed in the naive cell populations synchronous oscillations in [Ca2+]i concentration during this second phase (amplitude, 10-60 nM; frequency, 1-3/100 sec). These oscillations were maintained through extracellular calcium (EC Ca2+) entry; the initial peak was the result of Ca2+ release from intracellular stores. In desensitized cells, these two phases could not be clearly separated with respect to Ca2+ source, but, as we showed before, exhibited an enhanced dependence on EC Ca2+ entry for the response to PTH. Nevertheless, in the desensitized cells, the sustained [Ca2+]i response was diminished in magnitude and showed little oscillatory behavior. Brief exposure to neomycin sulfate, an inhibitor of phosphoinositide turnover, attenuated the PTH-induced [Ca2+]i rise in both naive and desensitized cells. Protein kinase-C activity did not appear to be required for either phase of the PTH-induced [Ca2+]i response. Exposure to cholera toxin attenuated the [Ca2+]i response to hormone in both naive and desensitized cells, more markedly in the latter. Cholera toxin treatment dramatically increased basal cAMP levels in both cell preparations; PTH-stimulated cAMP production was unchanged in naive cells, but increased nearly 4-fold in desensitized cells. We propose that the preserved PTH-induced peak [Ca2+]i rise in desensitized cells results primarily from the diminished regulation of EC Ca2+ entry by the cAMP response limb. The attenuated sustained oscillatory behavior observed in desensitized cells upon rechallenge with hormone may be the result of reduced phosphoinositide turnover and reduced Ca2+-stimulated Ca2+ release. Thus, the [Ca2+]i response to PTH in osteoblast-like cells is complex and modulable and seems to provide a number of ways to regulate intracellular metabolism under various conditions. We speculate that this plasticity of the [Ca2+]i response to PTH is related to the pleiotropic actions of the hormone on cells of the osteoblast lineage.
Endocrinology 1991 Dec
PMID:Parathyroid hormone (PTH)-induced intracellular Ca2+ signalling in naive and PTH-desensitized osteoblast-like cells (ROS 17/2.8): pharmacological characterization and evidence for synchronous oscillation of intracellular Ca2+. 195 83

Previous studies demonstrated that tetracyclines (TCs) inhibited Type I (interstitial) and Type IV collagenases from different mammalian sources, but there are no studies of TCs effect on osteoblast collagenase (C'ase). The present study assessed the effect of TCs on C'ase activity from osteosarcoma cells. Semiconfluent UMR 106-01 cells were treated with minocycline or chemically modified tetracycline (CMT) at 10 micrograms/ml in the presence or absence of bovine parathyroid hormone, b-PTH-(1-34), at 10(-7)M for 24, 48, 72 and 96 hours. Media were collected at each time point and assayed following concentration, destruction of TIMP by reduction/alkylation, activation with p-aminophenylmercuric acetate (APMA), and incubation with 3H-methylated collagen substrate (approximately 100,000 dpm) at 27 degrees C for 18 hours. Collagenase activity from media was also analyzed by SDS-PAGE and fluorography. b-PTH appeared to stimulate C'ase 60-fold compared to controls; minocycline and CMT reduced PTH stimulation approximately 65% and 90%, respectively. Moreover, TCs incubated with partially purified osteoblastic collagenase directly, inhibited its activity in vitro as indicated by a lack of degradation to collagen alpha A chains. Therefore, TCs ability to inhibit bone resorption in organ culture, reported previously, may be due, in part, to reduced osteoblast collagenase activity.
Res Commun Chem Pathol Pharmacol 1990 Dec
PMID:The effect of tetracyclines on collagenase activity in UMR 106-01 rat osteoblastic osteosarcoma cells. 196 17


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