Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduced glutathione (gamma-glutamylcysteinylglycine, GSH) plays an important role in the protection of cells against damage from free radicals and other electrophils and also influences cellular radiosensitivity, cellular response to hyperthermia, and cytotoxicity to some kinds of chemotherapeutic agents. The concentrations of GSH in 40 primary and metastatic brain tumors were quantitatively analyzed, and GSH was localized in these tumors by a novel o-phthalaldehyde histofluorescence method. The level of GSH was 195.2 +/- 57.1 micrograms/gm (mean +/- standard deviation) in glioblastomas multiforme, 444.1 +/- 105.1 micrograms/gm in normal brain tissues, and 614.4 +/- 237.4 micrograms/gm in meningiomas. The differences in GSH levels between glioblastomas and normal brain tissues and between glioblastomas and meningiomas were statistically significant (p less than 0.01). The mean GSH level in astrocytoma grades II and III was 321.9 +/- 11.8 micrograms/gm. The difference in the GSH level between glioblastomas and astrocytomas was statistically significant (p less than 0.05). Radiosensitive tumors, such as multiple myeloma, germinoma, and small-cell carcinoma, showed low GSH levels. These data suggest the possibility that the GSH may be a predictor for the efficacy of radiation therapy. The cytochemical study showed GSH localized in the cytoplasm; although it stained well in meningioma tissue, GSH was not well stained in sections of multiple myeloma. The endothelial proliferation did not stain well in glioblastoma, which seems to imply that this area is vulnerable to attack by free radicals from irradiation and/or chemotherapy.
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PMID:Quantitative analysis of glutathione in human brain tumors. 169 Jul 92

Monoclonal antibodies to ligandin (YaYa) and glutathione (GSH) S-transferase B (YaYc) were produced by hybridomas derived from the fusion of mouse myeloma cells and spleen cells of mice immunized with the YaYa or YaYc proteins, respectively. Enzyme-linked immunosorbent assay was used to screen for antibody-producing clones. Immunoblotting of the subunits of transferase B, ligandin, and another GSH S-transferase containing Yb subunits showed that the monoclonal antibodies produced by two anti-YaYa subclones recognized the Ya subunits of both ligandin and transferase B, but they did not bind Yc or Yb subunits. It was also revealed that antibodies produced by several anti-YaYc subclones recognized the Yc subunit, but not the Ya subunit of the antigen which was used for the immunization of the mice. However, these monoclonal antibodies did bind the Ya subunit of ligandin. These results indicate that the Ya subunits of GSH S-transferase B and of ligandin do share at least one common determinant. However, these two Ya subunits are structurally distinct as evidenced by their differences in binding by monoclonal anti-YaYc antibodies.
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PMID:Multiple Ya subunits of glutathione S-transferase detected by monoclonal antibodies. 242 Feb 77

Multidrug resistance (MDR) is a phenomenon associated with the emergence of simultaneous cross-resistance to the cytotoxic action of a wide variety of structurally and functionally unrelated antineoplastic agents. The present study was undertaken to determine if 8226 human myeloma cells possessing the MDR phenotype had an increased ability to resist the intercalating drug doxorubicin (DOX) via glutathione-based detoxification systems. Glutathione S-transferase (GST) was isolated by affinity chromatography, and the enzyme activity was assessed using 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione (GSH) as substrates. There was no difference in overall GST activity between the sensitive and resistant cells. Using a cDNA probe (pGTSS1-2) for the human placental, anionic GST isoenzyme, no overexpression of mRNA for this isoenzyme was noted in the resistant line. When glutathione peroxidase activity (GSH-px) was assessed using either H2O2 or cumene hydroperoxide as substrate, again there was no difference in enzyme activity. Non-protein sulfhydryl (NPSH) levels were found to be elevated significantly in the resistant 8226/DOX40 subline (19.2 +/- 0.1 nmol NPSH/10(6) cells) as compared to the drug-sensitive parental subline 8226/S (11.6 +/- 1.9 nmol NPSH/10(6) cells) (P less than 0.001). In addition, when the 8226/DOX40 cells were cultured in medium without doxorubicin, there was a consistent decline in NPSH values reaching a steady state identical to that of the 8226/S cells. However, the decrease in NPSH level was not accompanied by a change in the level of doxorubicin resistance as assessed by colony-forming assays. Depletion of glutathione by D,L-buthionine-S,R-sulfoximine had no effect on doxorubicin sensitivity in either subline. Thus, it appears that GSH-based detoxification systems are not causally involved in maintaining the MDR phenotype in 8226 human myeloma cells; rather they appear to comprise an epiphenomenon associated with the resistance selection procedure.
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PMID:Role of glutathione and its associated enzymes in multidrug-resistant human myeloma cells. 293 May 79

Splenic lymphocytes from mice immunized with a partially purified prostaglandin (PG) H-PGE isomerase from sheep vesicular glands were fused with SP2/0-Ag14 myeloma cells. Two spleen cell-myeloma hybrids (hei-7 and hei-26) were selected and cloned. The mouse antibodies secreted by the two hybrids, IgG1 (hei-7) and IgG1 (hei-26), caused immunoprecipitation of a maximum of 45 and 22%, respectively, of the solubilized PGH-PGE isomerase activity of sheep vesicular gland; immunoprecipitation of activity by the two antibodies was additive. The antigens reactive with IgG1 (hei-7) and IgG1 (hei-26) were identified as proteins with Mr = 17,500 and 180,000, respectively, by Western transfer blotting or sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitated 125I-labeled microsomes. The PGH-PGE isomerase activities precipitated by IgG1 (hei-7) and IgG1 (hei-26) exhibited different kinetic properties with respect to time course, Km for PGH2, and concentration dependence for GSH. No significant GSH-S-transferase activity was present in these immunoprecipitates. These data indicate that there are at least two different proteins in sheep vesicular gland microsomes capable of catalyzing GSH-dependent PGH-PGE isomerase reactions. IgG1 (hei-7), but not IgG1 (hei-26), caused coprecipitation of PGH synthase and PGH-PGE isomerase activities when incubated with intact right-side-out vesicular gland microsomes. Thus, the epitope for IgG1 (hei-7) is located on the cytoplasmic surface of those microsomal spheres which contain PGH synthase. This latter finding suggests that the isomerase reactive with IgG1 (hei-7) is involved in PGE synthesis in sheep vesicular glands.
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PMID:Immunochemical and kinetic evidence for two different prostaglandin H-prostaglandin E isomerases in sheep vesicular gland microsomes. 310 May 31

The glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO) was tested for cytotoxicity and thiol depletion in murine and human tumor cells in vitro, and for its antitumor activity and toxicity in vivo. The cell lines used in these studies included murine L-1210 leukemia, human RPMI 8226 myeloma, MCF-7 breast cancer and WiDr colon carcinoma. Soft agar colony forming assays showed that BSO was most effective at reducing tumor colony formation when exposed continuously to cells in vitro. Drug concentrations which inhibited colony formation to 50% of control levels ranged from 2.0-6.2 mM (for 1 hour exposures), 2-100 mM for 24 hour exposures and 0.4-1.40 microM (for continuous BSO exposures). Human myeloma cells proved most sensitive to BSO. In vitro cytotoxicity correlated with depletion of intracellular nonprotein sulfhydryls to less than or equal to 10% of control values in both L-1210 and 8226 cells. This was routinely achieved with prolonged exposures to mM BSO concentrations for greater than 24 hours. Normal mice tolerated high BSO doses (up to 5.0 g/kg) without evidence of acute toxicity. BSO was not active against L-1210 leukemia-bearing DBA/2 mice. When tested in vivo against MOPC-315 plasmacytoma-bearing BALB/c mice, BSO was not active at doses up to 4.0 g/kg. In contrast, the bifunctional alkylating agent melphalan (L-PAM) was active against MOPC-315 and this activity was enhanced by a 24 hour pretreatment of mice with 50 mg/kg of L-BSO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic effects of glutathione synthesis inhibition by L-buthionine-(SR)-sulfoximine on human and murine tumor cells. 358 42

A serum-free medium was developed for culture of plasmacytomas and hybridomas that are dependent upon or independent of the presence of specific P388D1-derived polypeptide growth factors. Possibly due to the stringency of requirements for culturing such plasmacytomas, a highly advantageous combination of components was developed. The medium, SFM, contains RPMI 1640, beta-mercaptoethanol, Hepes buffer, reduced glutathione (GSH), selenite (Se), pyruvate, transferrin, albumin, soybean lipids, and low density lipoproteins. A cooperative effect of GSH and Se is observed. SFM supports the continuous, prodigious growth of every B cell line tested, including a variety of the plasmacytomas, hybridomas, myeloma fusion partners and lymphoma cell lines, as well as the macrophage-like cell line P388D1. All of the B cell lines grow equally as well in SFM as in serum-containing medium. Hybridoma lines from mouse-mouse and rat-mouse fusions continue to produce monoclonal antibodies which can then be purified in a single-step procedure. The cells can be cloned out and frozen down in SFM. In addition, the medium is highly effective for establishment of plasmacytoma cell lines from some transplantable plasmacytomas, including early generation tumors.
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PMID:Serum-free medium for growth factor-dependent and -independent plasmacytomas and hybridomas. 358 96

Red cell reduced glutatione (GSH) and pyrimidine 5'-nucleotidase (Pry 5'-NT) were measured in a variety of myeloproliferative and lymphoproliferative disorders. Raised levels of GSH were found in chronic lymphocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, Waldenstrom's macroglobulinaemia and myeloma. Decreased activity of Pyr 5'-NT was found in acute myeloblastic leukaemia, acute lymphoblastic leukaemia, chronic granulocytic leukaemia, chronic lymphocytic leukaemia, Hodgkin's disease and non-Hodgkin's lymphoma. There was no correlation between the raised GSH levels and decrease Pry 5'-NT levels.
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PMID:Red cell pyrimidine 5'-nucleotidase and glutathione in myeloproliferative and lymphoproliferative disorders. 624 15

Levels of intracellular glutathione (GSH) and the GSH-related enzymes gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyltranspeptidase (gamma-GT) were measured in the melphalan-resistant human multiple myeloma cell line 8226/LR-5 and were compared to those measured in the drug-sensitive 8226/S and doxorubicin-resistant 8226/Dox40 cell lines. Both GSH and gamma-GCS activity, the rate-limiting step in the de novo synthesis of GSH, were elevated by a factor of approximately 2 in the melphalan-resistant 8226/LR-5 cells relative to the other two lines. gamma-GT activity was not elevated significantly in the /LR-5 cells. Northern analysis with a probe specific for the large subunit of human liver gamma-GCS identified two bands (3.2 and 4.0 kb), both of which were increased by a factor of 2-3 in the 8226/LR-5 line. Levels of gamma-GCS mRNA expression were comparable in the /S and /Dox40 cell lines. Levels of gamma-GT mRNA were similar in the /S and /LR-5 lines but were reduced in the /Dox40 cells. These data suggest that the increased GSH levels associated with resistance to melphalan in the 8226/LR-5 myeloma cells is attributable to up-regulation of gamma-GCS. This observation is consistent with recent demonstrations of up-regulation of gamma-GCS in melphalan-resistant prostate carcinoma cells and cisplatinum-resistant ovarian carcinoma cells, suggesting that increased expression of gamma-GCS may be an important mediator of GSH-associated resistance mechanisms.
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PMID:Up-regulation of gamma-glutamylcysteine synthetase activity in melphalan-resistant human multiple myeloma cells expressing increased glutathione levels. 751 21

Sensitivity to nickel, cobalt, and chromium is common among the general population. The identification of these sensitivities is generally by the detection of cell-mediated immunity. We have reported previously the use of an indirect enzyme-linked immunosorbent assay method to quantitate metal-specific antibodies in patients with total joint replacements. To study the haptenic potential of these metal ions, rabbit albumin-glutathione-metal complexes with chromium, cobalt, or nickel were injected into mice. The splenocytes from one mouse in each group which developed a strong antibody against GSH-metal complexes were isolated and fused with myeloma cells to produce monoclonal antibodies. Chromium, cobalt, and nickel antibodies had similar affinity and bound with the specific GSH-metal complex. There was very little cross-reactivity between these antibodies. An inhibition assay using these monoclonal antibodies was demonstrated to be a simple technique, suitable for quantitation of free metal in solution.
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PMID:Production of monoclonal antibodies to study corrosion products of CO-CR biomaterials. 873 Nov 51

Both alpha-linolenic (ALA) and eicosapentaenoic acids (EPA) were toxic to SP 2/0 mouse myeloma cells in vitro. On the other hand, linoleic acid (LA), gamma-linolenic acid (GLA), di-homo-gamma linolenic acid (DGLA), arachidonic acid (AA), docosahexaenoic acid (DHA) and oleic acid (OA) were much less effective in their growth suppressive actions. Both nordihydroguaiaretic acid (NDGA) and Indomethacin (IM) could block the action of the fatty acids indicating a role for prostaglandins (PGs) and leukotrienes (LTs) in the growth suppressive action of ALA and EPA. Superoxide dismutase (SOD) completely blocked, while vitamin E and reduced glutathione (GSH) could prevent to a limited extent the anti-proliferative effects of ALA and EPA. Catalase, mannitol, chlorpromazine (CPZ) and trifluoperazine (TFP) did not block the cytotoxic actions of ALA and EPA. N(G)-mono-methyl L-arginine (N(G)MMA), an analogue of L-arginine, which inhibits nitric oxide synthase, was ineffective in preventing the cytotoxicity induced by ALA and EPA. Fatty acid analysis of the various lipid fractions of SP 2/0 cells treated with ALA and EPA showed significant incorporation of these fatty acids in the cell membrane lipid pools. These results suggest that ALA and EPA induced suppression of SP 2/0 cell proliferation is cyclo-oxygenase (CO), lipoxygenase (LO) and superoxide dependent. Lipid peroxidation has only a limited role in this process. Both calmodulin dependent process and L-arginine derived nitric oxide do not seem to have a role in the cytotoxic action of ALA and EPA in these cells.
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PMID:Cytotoxic action of alpha-linolenic and eicosapentaenoic acids on myeloma cells in vitro. 915 Mar 74


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