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Janine P Wereley - One of the best experts on this subject based on the ideXlab platform.
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resistance to the antitumor agent Gallium nitrate in human leukemic cells is associated with decreased Gallium iron uptake increased activity of iron regulatory protein 1 and decreased ferritin production
Journal of Biological Chemistry, 1997Co-Authors: Christopher R. Chitambar, Janine P WereleyAbstract:Abstract The mechanism of drug resistance to Gallium nitrate is not known. Since Gallium can be incorporated into ferritin, an iron storage protein that protects cells from iron toxicity, we investigated whether ferritin expression was altered in Gallium-resistant (R) CCRF-CEM cells. We found that the ferritin content of R cells was decreased, while heavy chain ferritin mRNA levels and iron regulatory protein-1 (IRP-1) RNA binding activity were increased. IRP-1 protein levels were similar in Gallium-sensitive (S) and R cells, indicating that R cells contain a greater proportion of IRP-1 in a high affinity mRNA binding state. 59Fe uptake and transferrin receptor expression were decreased in R cells. In both S and R cells, Gallium inhibited cellular 59Fe uptake, increased ferritin mRNA and protein, and decreased IRP-1 binding activity. Gallium uptake by R cells was markedly diminished; however, the sensitivity of R cells to Gallium could be restored by increasing their uptake of Gallium with excess transferrin. Our results suggest that R cells have developed resistance to Gallium by down-regulating their uptake of Gallium. In parallel, iron uptake by R cells is also decreased, leading to changes in iron homeostasis. Furthermore, since Gallium has divergent effects on iron uptake and ferritin synthesis, its action may also include a direct effect on ferritin mRNA induction and IRP-1 activity.
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evaluation of transferrin and Gallium pyridoxal isonicotinoyl hydrazone as potential therapeutic agents to overcome lymphoid leukemic cell resistance to Gallium nitrate
Clinical Cancer Research, 1996Co-Authors: Christopher R. Chitambar, Pamela Boon, Janine P WereleyAbstract:Gallium nitrate is active against lymphoma and bladder cancer; however, little is understood about tumor resistance to this drug. Transferrin, the iron transport protein, increases Gallium uptake by cells, whereas pyridoxal isonicotinoyl hydrazone (PIH), an iron chelator, transports iron into cells. Therefore, we examined whether these metal transporters would increase the cytotoxicity of Gallium in Gallium nitrate-resistant CCRF-CEM cells. Transferrin, in increasing concentrations, enhanced the cytotoxicity of Gallium nitrate. One mg/ml transferrin decreased the 50% inhibitory concentration of Gallium nitrate from 1650 to 75 micrometer in Gallium-resistant cells and from 190 to 150 micrometer in Gallium-sensitive cells. Transferrin also enhanced the cytotoxicity of Gallium even at drug concentrations that were not growth inhibitory. The Gallium chelate Ga-PIH inhibited the growth of both Gallium nitrate-resistant and -sensitive cells. Fifty micrometer Ga-PIH inhibited cellular proliferation by 50%, whereas similar concentrations of PIH or Gallium nitrate were not growth inhibitory. However, because higher concentrations of PIH also inhibited cell growth, the cytotoxicity of Ga-PIH was greater than PIH only at concentrations of <100 micrometer. Cross-titration experiments demonstrated that the cytotoxicity of PIH was partially reversed by Gallium nitrate, whereas the cytotoxicity of Gallium nitrate was enhanced by PIH. Our studies suggest that Ga-PIH warrants further evaluation as a potential antineoplastic agent. Because transferrin increases the cytotoxicity of Gallium nitrate in transferrin receptor-bearing, Gallium nitrate-resistant cells, future clinical trials of this drug should incorporate the development of strategies to increase plasma transferrin levels.
Christopher R. Chitambar - One of the best experts on this subject based on the ideXlab platform.
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resistance to the antitumor agent Gallium nitrate in human leukemic cells is associated with decreased Gallium iron uptake increased activity of iron regulatory protein 1 and decreased ferritin production
Journal of Biological Chemistry, 1997Co-Authors: Christopher R. Chitambar, Janine P WereleyAbstract:Abstract The mechanism of drug resistance to Gallium nitrate is not known. Since Gallium can be incorporated into ferritin, an iron storage protein that protects cells from iron toxicity, we investigated whether ferritin expression was altered in Gallium-resistant (R) CCRF-CEM cells. We found that the ferritin content of R cells was decreased, while heavy chain ferritin mRNA levels and iron regulatory protein-1 (IRP-1) RNA binding activity were increased. IRP-1 protein levels were similar in Gallium-sensitive (S) and R cells, indicating that R cells contain a greater proportion of IRP-1 in a high affinity mRNA binding state. 59Fe uptake and transferrin receptor expression were decreased in R cells. In both S and R cells, Gallium inhibited cellular 59Fe uptake, increased ferritin mRNA and protein, and decreased IRP-1 binding activity. Gallium uptake by R cells was markedly diminished; however, the sensitivity of R cells to Gallium could be restored by increasing their uptake of Gallium with excess transferrin. Our results suggest that R cells have developed resistance to Gallium by down-regulating their uptake of Gallium. In parallel, iron uptake by R cells is also decreased, leading to changes in iron homeostasis. Furthermore, since Gallium has divergent effects on iron uptake and ferritin synthesis, its action may also include a direct effect on ferritin mRNA induction and IRP-1 activity.
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modulation of in vitro and in vivo t cell responses by transferrin Gallium and Gallium nitrate
Blood, 1996Co-Authors: William R Drobyski, Riaz Ulhaq, David Majewski, Christopher R. ChitambarAbstract:Gallium is a group IIIa metal that has efficacy in the therapy of malignant disorders such as lymphoma and urothelial tract tumors. Preclinical studies also indicate a role for Gallium in autoimmune disorders, suggesting that Gallium is able to modulate T-cell immune reactivity. The purpose of this study was to examine the in vitro and in vivo immunomodulatory action of Gallium on T-cell function. Since Gallium binds to transferrin in vivo, in vitro studies evaluated the effect of transferrin-Gallium (Tf-Ga) on human T cells. Tf-Ga inhibited the mitogen-induced proliferative response of peripheral blood mononuclear cells (PBMC) in a dose-dependent fashion. Alloantigen-induced proliferation was also potently suppressed when evaluated in a mixed lymphocyte culture assay. Tf-Ga affected a significant reduction in the density of IL-2 receptors on activated T cells and a slight reduction in the number of CD3+/CD25+ T cells in PHA-stimulated cultures. Neither secretion of interleukin-2 (IL-2) nor the induction of IL-2-stimulated lymphokine-activated killer activity, however, was inhibited by Tf-Ga. Tf-Ga produced significant upregulation of the transferrin receptor (CD71) in T cells as determined by flow cytometric analysis and northern blot assay, but did not affect the percentage of CD3+/ CD71+ T cells after mitogen stimulation. To assess the in vivo effects of Gallium on alloreactive T cells, we evaluated the immunosuppressive effect of Gallium in a murine model of graft-versus-host disease (GVHD). Administration of Gallium significantly prolonged survival in mice undergoing severe GVHD, suggesting that Gallium can ameliorate GVH reactivity. Collectively, these data demonstrate that, at clinically achievable concentrations, Tf-Ga potently inhibits T-cell activation and that this immunosuppressive property of Gallium may be of adjunctive therapeutic value in the management of disorders characterized by the presence of autoreactive or alloreactive T-cell populations.
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evaluation of transferrin and Gallium pyridoxal isonicotinoyl hydrazone as potential therapeutic agents to overcome lymphoid leukemic cell resistance to Gallium nitrate
Clinical Cancer Research, 1996Co-Authors: Christopher R. Chitambar, Pamela Boon, Janine P WereleyAbstract:Gallium nitrate is active against lymphoma and bladder cancer; however, little is understood about tumor resistance to this drug. Transferrin, the iron transport protein, increases Gallium uptake by cells, whereas pyridoxal isonicotinoyl hydrazone (PIH), an iron chelator, transports iron into cells. Therefore, we examined whether these metal transporters would increase the cytotoxicity of Gallium in Gallium nitrate-resistant CCRF-CEM cells. Transferrin, in increasing concentrations, enhanced the cytotoxicity of Gallium nitrate. One mg/ml transferrin decreased the 50% inhibitory concentration of Gallium nitrate from 1650 to 75 micrometer in Gallium-resistant cells and from 190 to 150 micrometer in Gallium-sensitive cells. Transferrin also enhanced the cytotoxicity of Gallium even at drug concentrations that were not growth inhibitory. The Gallium chelate Ga-PIH inhibited the growth of both Gallium nitrate-resistant and -sensitive cells. Fifty micrometer Ga-PIH inhibited cellular proliferation by 50%, whereas similar concentrations of PIH or Gallium nitrate were not growth inhibitory. However, because higher concentrations of PIH also inhibited cell growth, the cytotoxicity of Ga-PIH was greater than PIH only at concentrations of <100 micrometer. Cross-titration experiments demonstrated that the cytotoxicity of PIH was partially reversed by Gallium nitrate, whereas the cytotoxicity of Gallium nitrate was enhanced by PIH. Our studies suggest that Ga-PIH warrants further evaluation as a potential antineoplastic agent. Because transferrin increases the cytotoxicity of Gallium nitrate in transferrin receptor-bearing, Gallium nitrate-resistant cells, future clinical trials of this drug should incorporate the development of strategies to increase plasma transferrin levels.
Masumi Kadoya - One of the best experts on this subject based on the ideXlab platform.
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hilar and pancreatic Gallium 67 accumulation is characteristic feature of autoimmune pancreatitis
Pancreas, 2003Co-Authors: Hisanobu Saegusa, Mitsuhiro Momose, Shigeyuki Kawa, Hideaki Hamano, Yasuhide Ochi, Mari Takayama, Kendo Kiyosawa, Masumi KadoyaAbstract:Introduction and aims Autoimmune pancreatitis is characterized by severe lymphocytic inflammation, suggesting that Gallium-67 scintigraphy provides a useful tool for detecting characteristic lesions of this disease, because Gallium-67 concentrates in lymphoid cells. We tried to determine whether Gallium-67 accumulates in the characteristic lesions. Methodology We performed Gallium-67 scintigraphy in 24 patients with autoimmune pancreatitis before and after 4 weeks of corticosteroid therapy and determined the factors associated with positive images. Results Sixteen patients (67%) had marked Gallium-67 accumulation in the pancreas before corticosteroid therapy and negative images after 4 weeks of therapy, and they had significantly higher serum IgG4 values than did those without Gallium-67 accumulation (median, 758 mg/dL versus 329 mg/dL; p = 0.011). Marked hilar Gallium-67 accumulation was found in 16 patients (67%) and was also associated with significantly higher serum IgG4 values than did those without it (median, 758 versus 239 mg/dL; p = 0.0044). Among 16 patients with positive hilar images, 12 had positive pancreatic uptake and 5 had both pancreatic and salivary gland uptakes. Conclusions Hilar and pancreatic accumulation of Gallium-67 is a characteristic feature of autoimmune pancreatitis during the active stage of the disease, when IgG4 serum levels are high.
Ronald D Neumann - One of the best experts on this subject based on the ideXlab platform.
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positive Gallium 67 citrate scintigraphy in wiskott aldrich syndrome with malignant lymphoma
European Journal of Nuclear Medicine and Molecular Imaging, 1991Co-Authors: Dirk Sandrock, Secondo Lastoria, Maria J Merino, Ronald D NeumannAbstract:This case describes the first detection of solid lymphoma lesions by Gallium-67 scintigraphy in a 12-year-old patient with Wiskott-Aldrich syndrome. Gallium 67 uptake was found in multiple sites in the patient who had developed an undifferentiated small, noncleaved cell lymphoma. Response to chemotherapeutic treatment is correlated with findings on the Gallium scintigraphy follow-up.
Baldomero Garcia - One of the best experts on this subject based on the ideXlab platform.
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indium Gallium nitride multijunction solar cell simulation using silvaco atlas
2007Co-Authors: Baldomero GarciaAbstract:Abstract : This thesis investigates the potential use of wurtzite Indium Gallium Nitride as photovoltaic material. Silvaco Atlas was used to simulate a quad-junction solar cell. Each of the junctions was made up of Indium Gallium Nitride. The band gap of each junction was dependent on the composition percentage of Indium Nitride and Gallium Nitride within Indium Gallium Nitride. The findings of this research show that Indium Gallium Nitride is a promising semiconductor for solar cell use.
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indium Gallium nitride multijunction solar cell simulation using silvaco atlas
2007Co-Authors: Baldomero GarciaAbstract:Abstract : This thesis investigates the potential use of wurtzite Indium Gallium Nitride as photovoltaic material. Silvaco Atlas was used to simulate a quad-junction solar cell. Each of the junctions was made up of Indium Gallium Nitride. The band gap of each junction was dependent on the composition percentage of Indium Nitride and Gallium Nitride within Indium Gallium Nitride. The findings of this research show that Indium Gallium Nitride is a promising semiconductor for solar cell use.
