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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron, apart a for long time well-known function connected with: transportation (hemoglobin), storage (myoglobin), and utilize (cytochromes, cytochrome oxidase) oxygen for respiration, has a critical role in host-pathogen interactions. Iron is essential for microbial growth, but also for immune function. The role of iron in infection, thermoregulation, acute lymphocytic leukemia, neoplasia, rheumatoid arthritis, stimulation of free radical reactions, and studies with iron chelation therapy are discussed.
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PMID:[The role of iron in immunologic processes]. 129 87

Chromophobe cell carcinoma is a little known variety of renal cell carcinoma representing 7 to 9% of all renal tumors. This tumor is confused with either clear cell carcinoma (clear subvariety) or oncocytoma (eosinophilic subvariety). Until ultrastructural and prospective studies of the prognosis of this tumor become available, it already seems important to perform colloidal iron staining to establish the differential diagnosis between oncocytoma and chromophobe cell carcinoma.
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PMID:[Is it useful to isolate a chromophobe cell variant among carcinomas of the kidney?]. 130 10

An important source of endogenous oxygen radicals are phagocytic cells such as neutrophils and macrophages. The human leukemia cell line HL-60 can be induced to differentiate into a neutrophil-like cell population. Among the properties of these differentiated cells is the ability to produce reactive oxygen species when stimulated by tumor promoters. Mutagenesis induced by HL-60-generated free radicals was assessed using the M13mp2 forward mutation assay. Single-stranded M13mp2 DNA was coincubated with phorbol ester-stimulated HL-60 cells, after which mutations were scored by transfecting the DNA into SOS-induced Escherichia coli. The mutation frequency was increased 6-fold above background in DNA incubated with HL-60 cells. The majority of the mutations were single-base substitutions. However, approximately 6% of the mutations were tandem double substitutions that occurred in runs of adjacent cytidines. Overall, the mutations were clustered at apparent "hot spots," many of which were similar to sites seen using iron to generate oxygen radicals. These results suggest that human cells able to produce oxygen radicals in response to tumor promoters might play a significant role in the generation of tumors.
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PMID:Mutagenic specificity of oxygen radicals produced by human leukemia cells. 131 Jun 39

Evidence is presented that the nitroxide free radical, TEMPO, at concentrations commonly used to prevent oxidative damage, increases the intracellular hydrogen peroxide concentration. To investigate the origin of this increased hydrogen peroxide concentration, we have incubated various human tumor cell lines with compounds interfering with the generation of active oxygen metabolites. Sodium azide, inhibitor of the respiratory chain, the iron-chelating agent desferrioxamine, superoxide dismutase and catalase had no effect on the hydrogen peroxide concentration. Metyrapone, inhibitor of the cytochrome P450 system, was demonstrated to decrease, but not completely prevent, the hydrogen peroxide production. N-ethylmaleimide, a sulphydryl-bond alkylating agent, was able to completely prevent the increased hydrogen peroxide production. We conclude that, by increasing the cellular hydrogen peroxide concentration, TEMPO exerts a pro-oxidant effect. This increase in hydrogen peroxide production seems to be mediated by the induction of oxidase activity in the cytochrome P450 system, but other cellular systems involved in electron transport may also play a role.
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PMID:Increased hydrogen peroxide concentration in human tumor cells due to a nitroxide free radical. 132 9

Gallium, when bound to transferrin, has been previously shown to cause tumor cell cytotoxicity by preventing cellular uptake of transferrin bound iron in vitro. Patients treated with constant infusion gallium nitrate for carcinoma show a rise in serum iron within 6 hr of the start of treatment. Serum iron returns to baseline by 24 hr post-infusion. Atomic analysis of iron and gallium content of Sephadex G-150 fractions of treatment sera indicate that about an equimolar amount of gallium and iron are associated with transferrin. These gallium and iron concentrations result in inhibition of transferrin mediated iron uptake in vitro, and in vivo allow for > 90% saturation of transferrin with metal. All seven patients who completed two courses of gallium therapy exhibited hypochromic microcytic anemia (mean fall in hemoglobin 3.5 grams %). Evidence for red cell iron depletion was confirmed by an increase (mean 3.3-fold) in zinc protoporphyrin levels. Since transferrin receptor increases on gallium treated iron requiring cells in vitro, we assessed cell surface transferrin receptor on peripheral blood lymphocytes by measuring fluorescent transferrin receptor antibody binding. A population of highly transferrin receptor positive cells peaks at 48 hr into the infusion. DNA analysis as well as double staining indicate the majority of transferrin receptor positive cells are unstimulated B lymphocytes. These studies provide the first documentation that constant infusion gallium treatment results in significant interference with iron metabolism and evidence for tissue iron depletion in vivo. These changes may correlate with therapeutic effects of gallium such as tumor response.
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PMID:Treatment with gallium nitrate: evidence for interference with iron metabolism in vivo. 133 63

This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: (1) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.
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PMID:Oxygen radicals in ulcerative colitis. 135 59

Forty-one specimens of mucinous cystadenoma (MCA) of the ovary and 13 specimens of normal uterine endocervix were investigated histochemically using alcian blue pH 2.5-PAS, high iron diamine-alcian blue pH 2.5, galactose oxidase-Schiff reaction (GOS, for detection of gastric surface mucous cell mucins), paradoxical Concanavalin A staining (PCS, for detection of gastric gland cell mucins) and periodic acid-sodium borohydride-potassium hydroxide-PAS (PA-SB-PH-PAS) reaction (for detection of mucins of the large intestine). In addition, Grimelius staining was carried out to explore the distribution of endocrine cells. The MCAs contained abundant neutral mucins but a little acid mucins, whereas sulfomucins predominated in normal endocervices. Among the MCAs, 30, 26, 2 and 9 had tumor cells positive for GOS, PCS, PA-SB-PH-PAS and Grimelius stain, respectively. These results indicate that MCAs frequently contain tumor cells of the gastrointestinal type and endocrine cell type. Endocervical epithelia, on the other hand, lack reactivity for PCS, PA-SB-PH-PAS and Grimelius stain, although in 8 of the present specimens, the lining cells showed weak GOS reactivity.
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PMID:Histochemical demonstration of gastrointestinal mucins in ovarian mucinous cystadenoma. 137 63

Research and clinical observations during the past six decades have shown that: 1. Iron promotes cancer cell growth; 2. Hosts attempt to withhold or withdraw iron from cancer cells; and 3. Iron is a factor in prevention and in therapy of neoplastic disease. Although normal and neoplastic cells have similar qualitative requirements for iron, the neoplastic cells have more flexibility in acquisition of the metal. Excessive iron levels in animals and humans are associated with enhanced neoplastic cell growth. In invaded hosts, cytokine-activated macrophages increase intracellular ferritin retention of the metal, scavenge iron in areas of tumor growth, and secrete reactive nitrogen intermediates to effect efflux of nonheme iron from tumor cells. Procedures associated with lowering host intake of excess iron can assist in prevention and in management of neoplastic disease. Chemical methods for prevention of iron assimilation by neoplastic cells are being developed in experimental and clinical protocols. The antineoplastic activity of a considerable variety of chemicals, as well as of radiation, is modulated by iron. The present article focuses on recent findings and suggests directions for further cancer-iron research.
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PMID:Roles of iron in neoplasia. Promotion, prevention, and therapy. 138 34

In order to ascertain the antitumor properties of metal complexes, we have investigated their effect on hepatic DNA, RNA pools, and protein levels in rats bearing transplanted tumors by Dalton's Lymphoma cells because antitumor agents are directed against DNA, RNA transcription, and synthesis. These coordination complexes have been synthesized by the condensation of 2,6-diacetylpyridine with FaHh and DAP-Th2, thereafter they were complexed with nickel, cobalt, and iron. The structure of these metal complexes have been elucidated on the basis of IR, UV, NMR, Mass, EPR, and magnetic studies. The tumor-transplanted rats were treated with these metal complexes and ligands (2 ml of 1 mM sol/Kg body weight, s.c.) for two weeks to study their effect on DNA, RNA pools, and protein levels. The metal complexes have altered the hepatic DNA, RNA pools, and protein levels in the liver, kidney, and spleen of rats.
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PMID:Antitumor activity of some metal complexes: effect on hepatic DNA, RNA, and protein synthesis in rats bearing transplanted tumors by Dalton's lymphoma cells. 138 16

Bleomycin is a glycopeptide antibiotic with a unique mechanism of antitumor activity. The drug binds to guanosine-cytosine-rich portions of DNA via association of the "S" tripeptide and by partial intercalation of the bithiazole rings. A group of five nitrogen atoms arranged in a square-pyramidal conformation binds divalent metals including iron, the active ligand, and copper, an inactive ligand. Molecular oxygen, bound by the iron, can produce highly reactive free radicals and Fe(III). The free radicals produce DNA single-strand breaks at 3'-4' bonds in deoxyribose. This yields free base propenals, especially of thymine: cytotoxicity is cell-cycle-phase specific for G2 phase. In humans, bleomycin is rapidly eliminated primarily by renal excretion. This accounts for approximately half of a dose. In patients with renal compromise or extensive prior cisplatin therapy, the drug half-life can extend from 2 to 4 hours up to 21 hours. Thus, dose adjustments are needed when creatinine clearance is less than or equal to 3N mL/min. Finally, resistance to bleomycin in normal tissues can be correlated with the presence of a bleomycin hydrolase enzyme, which is in the cysteine proteinase family. The enzyme replaces a terminal amine with a hydroxyl, thereby inhibiting iron binding and cytotoxic activity. The low concentration of enzyme in the skin and lung may explain the unique sensitivity of these tissues to bleomycin toxicity. However, correlation of hydrolase levels with tumor cell sensitivity has thus far been negative.
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PMID:Bleomycin pharmacology: mechanism of action and resistance, and clinical pharmacokinetics. 138 41


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