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)

Osteoblasts possess a concentrative L-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependent ascorbate transporter located in the plasma membrane. The transporter is specific for ascorbate and stereoselective for L-ascorbate over D-isoascorbate. The present study examined the effects of ascorbate supplementation and deprivation on the activity of this transport system. L-ascorbate transport activity was determined by measuring uptake of the vitamin by ROS 17/2.8 osteosarcoma cells during 1 minute incubations with 5 microM L-[14C]ascorbate. The initial rate of L-[14C]ascorbate uptake by ROS 17/2.8 cells grown for 18 h in L-ascorbate-replete medium was 89 +/- 8 nmol/g protein per minute. Following removal of L-ascorbate from the growth medium, the initial rate of uptake increased within 6 h to 126 +/- 13 nmol/g protein per minute. Conversely, the initial rate of uptake by cells grown in ascorbate-free medium decreased following the addition of L-ascorbate, but not D-isoascorbate, to the medium. The effect of ascorbate pretreatment was specific for ascorbate transport in that preincubation of cultures with L-ascorbate did not affect uptake of 2-deoxy-D-glucose. Kinetic analysis revealed that modulation of ascorbate transport arose from changes in the apparent maximum rate of transport (Vmax) without changes in the affinity of the transport system for L-ascorbate. These experiments are the first to show that ascorbate transport by osteoblastic cells responds to vitamin C deprivation and supplementation. Adaptation of transport activity to substrate availability may play an important role in the physiological regulation of intracellular ascorbate levels.
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PMID:Adaptive regulation of ascorbate transport in osteoblastic cells. 141 86

The two naturally occurring forms of ricin A chain, Mr 33,000 and Mr 30,000 (RTA33 and RTA30) have been purified, and their chemical compositions, toxicities, and tissue distributions have been determined. As reported previously, the in vitro and in vivo toxicities of RTA30 and RTA33 are similar. However, RTA30, which contains less carbohydrate with a lower mannose content than RTA33, accumulated less in the liver than did RTA33. Monoconjugate immunotoxins (i.e., containing one RTA per monoclonal antibody molecule) were constructed between RTA30 or RTA33 and the antitumor monoclonal antibody 791T/36, which recognizes a Mr 72,000 antigen on osteosarcoma and colon carcinoma cells. The two immunotoxins had similar cytoxicities in vitro but differed substantially in their pharmacokinetics and tissue distributions in vivo in nude mice bearing C170 human colorectal carcinoma xenografts. The immunotoxin derived from RTA30 (IT30) accumulated less in the liver than the immunotoxin derived from RTA33 (IT33) and cleared more slowly from the blood; the alpha and beta half-lives for IT30 and IT33 were 0.50 and 20.5 versus 0.17 and 14.6 h, respectively. As a probable consequence, IT30 accumulated to approximately 3-fold higher levels in the C170 xenografts than IT33. The reduced clearance of IT30 by the reticuloendothelial system thus resulted in prolonged survival in the blood and enhanced tumor localization relative to IT33.
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PMID:Improved pharmacokinetics and tumor localization of immunotoxins constructed with the Mr 30,000 form of ricin A chain. 186 42

Assessment is made of the presence or absence of specific sugar receptors (lectins) in patients operated for intrapulmonary metastases of osteogenic sarcoma. Investigations were carried out on histochemically stained paraffin sections for the separate types of sugars. Highest was the presence of specific receptors for sialic acid and for N-acetylglucosamine, followed by those for ramnose and heparin and least for mannose and maltose. Lectin determination is a new branch in morphological science, assisting clinical practice, special surgical activity by the attempt for quantitative grading of cell populations in norm and in their neoplastic development.
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PMID:[An evaluation of endogenous lectins in the intrapulmonary metastases of osteogenic sarcoma]. 239 6

The in vitro and in vivo binding of a monoclonal antibody (MAB) that recognizes a tumor-associated carbohydrate antigen was studied in dogs. Monoclonal antibody 155H.7 was raised in response to innoculation of mice with beta-galactose(1-3)beta N-acetylgalactosamine conjugated to human serum albumin. Avidin-biotin-complex immunohistochemical staining of cryostat sections of normal and neoplastic canine tissue specimens revealed heterogenous binding of MAB 155H.7 to the cells of many canine mammary and lung carcinomas and homogenous staining of many sarcomas, including osteogenic sarcoma. In addition, there was variable staining of a variety of normal tissues including some ductual epithelium, peripheral nerve fibers, and some endothelial cells and fibroblasts. Immunoscintigraphy with 131I-labeled MAB 155H.7 was used to study the in vivo distribution of the antibody. The 131I-labeled MAB 155H.7 was administered to 1 clinically normal dog, 7 dogs with osteogenic sarcoma, 1 dog with undifferentiated sarcoma, and 2 dogs with mammary tumor. Scintigraphy revealed concentration of radioactivity in 8 of 10 tumor sites within 24 hours after MAB administration. The ratio of 131I in tumor sites to 131I in the surrounding normal tissues, compared with the similar ratio of 99mTc-labeled erythrocytes ranged from 1.1 to 4.3, in tumor vs normal tissue with a mean value of 2, confirming tumor localization of the radiolabeled MAB in excess of that associated with enhanced tumor vascularization.
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PMID:Immunohistochemical staining and radionuclide imaging of canine tumors, using a monoclonal antibody recognizing a synthetic carbohydrate antigen. 254 21

An 125I-labeled synthetic analog of bovine parathyroid hormone, [8-norleucine,18-norleucine,34-tyrosine]PTH-(1-34) amide ([Nle]PTH-(1-34)-NH2), purified by high-pressure liquid chromatography (HPLC), was employed to label the parathyroid hormone (PTH) receptor in cell lines derived from PTH target tissues: the ROS 17/2.8 rat osteosarcoma of bone and the CV1 and COS monkey kidney lines. After incubation of the radioligand with intact cultured cells, the hormone was covalently attached to receptors by using either a photoaffinity technique or chemical (affinity) cross-linking. In each case, covalent labeling was specific, as evidenced by a reduction of labeling when excess competing nonradioactive ligand was present. After covalent attachment of radioligand, membranes were prepared from the cells and solubilized in the nonionic detergent Nonidet P-40 or octyl glucoside. The soluble membrane fraction present in the supernatant of a 100,000 X g centrifugation was incubated with IgG prepared from anti-PTH antiserum generated to the amino-terminal region, residues 1-34, of PTH. The IgG-PTH-receptor complex was precipitated with staphylococcal protein A-Sepharose. Analysis of the immunoprecipitate on NaDod-SO4/polyacrylamide gel electrophoresis followed by autoradiography revealed the presence of a doublet of apparent molecular mass 69-70 kDa. Specifically labeled bands of approximate molecular mass 95 and 28 kDa were also observed. The anti-PTH IgG was affinity purified by passage over a PTH-Sepharose column and used to make an immunoaffinity column. The 70- and 28-kDa bands were also observed after labeled solubilized membrane preparations were allowed to bind to this column and then were eluted by using a [Nle]PTH-(1-34)-NH2-containing buffer or acetic acid. These studies suggest that the use of an anti-PTH antiserum that binds receptor-bound hormone is likely to be a useful step in the further physiochemical characterization and purification of the PTH receptor.
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PMID:Immunoprecipitation of the parathyroid hormone receptor. 302 60

Type V collagen from FBJ virus-induced osteosarcoma of mice has a high content of saccharide as has been noted for type V collagens from different sources. In the present study, this collagen was found to contain significant amounts of mannose and hexosamine. Three alpha chains of this collagen were electrophoretically separated and cleaved by cyanogen bromide. The cyanogen bromide peptides, following their separation by SDS-polyacrylamide gel electrophoresis, were transferred onto nitrocellulose paper and stained with concanavalin A. Several bands derived only from alpha 3(V) stained positively, but this was inhibited by the presence of alpha-methylmannoside. Thus, at least one of these three chains appears to have an asparagine-linked oligosaccharide.
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PMID:The staining of type V collagen obtained from FBJ virus-induced osteosarcoma with concanavalin A. 345 58

Since 1970, we have carried out cancer chemotherapy and immunotherapy in cooperation with Japanese scientists, particularly Prof. H. Umezawa, who has generously supplied bleomycin, peplomycin, acalcinomycin A (ACM), THP-adriamycin (THP), neothramycin and bestatin. Malignant tumors curable by pharmacotherapy are polycythemia vera (CR 100%), acute lymphoid leukemia (ALL) (CR 80%), Burkitt tumor (CR 80 or 50%), Hodgkin disease (CR 80%), chorioepithelioma (CR 80%), testicular cancer (CR 80%), ovary cancer of children (CR 80%), Wilms renal cancer (CR 60%), rhabdomyosarcoma (CR 75%), osteosarcoma (CR 60%), Ewing tumor (CR 60%), brain tumor of children (CR greater than 50%), testicular embryonal cancer of children (CR greater than 50%), acute myeloid leukemia (AML) (CR 50%), non-Hodgkin lymphoma (NHL) (CR 50%), ovary cancer of adults (CR 40%), small cell lung cancer (CR 20%) and breast cancer. Our experimental and/or clinical experience with ACM, THP, methoxy-9-ellipticine lactate, navelbine, 4-demethyl-epipodophyllotoxin-beta-d-ethyledene glucoside, bestatin and interferon is presented. ACM is effective against AML, ALL, NHL, Burkitt tumor, breast cancer. We have comparatively investigated cardiac and dermal toxicity of 12 kinds of anthracycline antibiotics and mitoxantrone, using golden hamsters. Of the drugs examined, ACM, THP, AD-32 and AD-143 cause much less cardiomyopathy and alopecia than the other agents. The results have been confirmed by electron microscopic studies. Bestatin is an immunorestorator, which recovers immunological functions decreased in aged animals. We hope that cancer chemotherapy and immunotherapy will progress in future and contribute to cure of neoplasms. Japanese scientists have been making a great contribution in the field of cancer pharmacotherapy, and we are eager to cooperate with Japanese scientists in cancer treatment studies.
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PMID:[Japanese-French cooperation in tumor pharmacotherapy: 1970-1990]. 619 71

MAb 50H.19 immunoprecipitates two proteins from lysates of human carcinoma cell lines, and embryonic fibroblasts intrinsically labelled with 3H-leucine, 35S-methionine, or a 3H-amino acid mixture; a major component of Mr = 22,000 (22 kd component) and a minor component of Mr = 24,000 (24 kd component). Oligomeric forms of the proteins are not observed under reducing or non-reducing conditions. Both proteins are expressed on the plasma membrane, and are glycoproteins. We investigated the relationship between the proteins in terms of their glycosylation and derivation from precursors. The 22 kd component is O-glycosylated as demonstrated by 3H-galactose incorporation, insensitivity to tunicamycin (TM), and its stepwise generation from a 20.5 kd precursor. The 24 kd protein is N-glycosylated, as shown by 3H-mannose incorporation, and by the total inhibition of its synthesis in the presence of TM. Further evidence for its N-glycosylation is provided by the appearance of a 23 kd precursor in lysates from the osteogenic sarcoma cell line SKOSC pulse-labelled for 5 min, a time preceding O-glycosylation of the 20.5 kd protein. Furthermore, mild alkali treatment of the immune complex leads to a loss of approximately 1,000 daltons in each glycoprotein confirming the O-glycosylated nature of the 22 kd component, and suggesting that the 24 kd component is additionally O-glycosylated. Both glycoproteins undergo an apparent increase of molecular weight of about 500 daltons when run in the non-reduced form on SDS polyacrylamide gels under standard electrophoretic conditions, suggesting they contain a similar degree of intra-chain disulphide bonding. Confirmatory evidence that the two components share a common polypeptide backbone is provided by the appearance of only the 20.5 kd component in lysates from SKOSC cells pulse-labelled for 5 min in the presence of TM.
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PMID:Biochemical characterization of human carcinoma surface antigen associated with protein kinase activity. 651 Nov 26

The effect of beta-all-trans-retinoic acid (RA) on the synthesis of cellular, cell surface, and secreted glycoconjugates by human Hs705 chondrosarcoma and Hs791 osteosarcoma cells was investigated in vitro. Untreated and RA-treated cells were labeled either metabolically with radioactive precursors or by oxidation of externally exposed cell membrane glycoprotein(s) (GP) by treatment with NalO4 or neuraminidase and galactose oxidase followed by reduction with NaB[3H]4. The cells were solubilized and analyzed by polyacrylamide gel electrophoresis followed by fluorography. RA enhanced the labeling of sialic acid and galactose residues on the GP of relative molecular weight(s) (Mr) in the range 95,000-300,000 on the surfaces of both cell types. [3H]glycosamine incorporation into GP with Mr of 100,000, 150,000, and 190,000 in both cell lines was also stimulated. In the Hs705 cells there was also an increase in the labeling of a 290,000-Mr GP. In contrast, [3H]glucosamine incorporation into glycoconjugates greater than 400,000 Mr in both the cells and the conditioned medium of Hs705 cells decreased. The latter glycoconjugates were susceptible to hyaluronidase and chondroitinases. [3H]glucosamine incorporation into a secreted 230,000-Mr GP, identified as fibronectin, was also reduced. Analyses of conditioned media of cells labeled with [35S]methionine or [14C]proline demonstrated that RA decreased the secretion of procollagen chains and fibronectin. Immunofluorescence revealed that RA alters the distribution of cell-associated fibronectin. These results demonstrated that RA increases the glycosylation of specific cellular and cell surface GP and decreases the production of secreted GP and glycosaminoglycans by the sarcoma cells.
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PMID:Modulation by retinoic acid of cellular, surface-exposed, and secreted glycoconjugates in cultured human sarcoma cells. 658 9

18F-2-fluoro-2-deoxy-D-glucose (FDG) is a novel radiopharmaceutical that has gained much interest as a cancer-seeking agent. In this paper two cases of histologically verified canine cancer, an osteosarcoma and a mammary carcinoma, are presented. After an intravenous bolus injection of FDG, accumulation of radioactivity over the neoplastic lesion was followed with a computer-guided specially collimated gamma camera. Ratios of radioactivity between tumour and control areas at 30 min were 2.8 and 2.2 for the osteosarcoma and the mammary carcinoma, respectively. In the osteosarcoma, which was imaged for 3 h, this ratio remained essentially stable. It is reasonable to assume that FDG will be suitable for cancer imaging in man.
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PMID:Imaging of canine cancers with 18F-2-fluoro-2-deoxy-D-glucose (FDG) suggests further applications for cancer imaging in man. 659 12


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