Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biologic evidence suggests that high body iron stores could promote development of cancer. Because a previous study had shown an association between prescribed iron medication and lung cancer risk in men, we examined recent iron use as well as 2 additional indirect measures of body iron stores, anemia and the total iron-binding capacity (TIBC) of plasma, in relation to subsequent risk of cancer in a larger cohort of 174,507 persons. Women, but not men, who reported recent iron use had a lower risk of lung cancer than those who did not [RR = 0.60, 95% confidence limits (CL) 0.37, 0.97] after adjustment for age and cigarette smoking. Women who had used iron appeared to remain relatively iron-depleted. Risk for other cancers was slightly, but not significantly, lower in women who used iron. Anemia (hemoglobin less than 12 g) was also associated with lower risk of lung cancer in women (RR = 0.61, 95% CL 0.61, 0.98), but not in men. TIBC, which is inversely related to body iron stores, was inversely related to risk of lung cancer in women in a graded fashion (RR = 0.41, 95% CL 0.23, 0.73 comparing highest with lowest quartile). In men, a protective effect of higher TIBC against lung cancer was suggested, but did not reach statistical significance. These indirect measures of body iron stores appeared to reflect iron stores better in women than in men, probably because variability in iron stores is greater in women and iron deficiency more prevalent. A possible alternative explanation for our findings is incomplete adjustment for the confounding effects of cigarette smoking. This could apply to iron use and hemoglobin level which were related to smoking, but not to TIBC, which was not. These data, which indicate lower risk of cancer in iron-depleted women, lend epidemiologic support to the hypothesis that high iron stores may increase cancer risk, at least for lung cancer.
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PMID:Epidemiologic evidence of an association between body iron stores and risk of cancer. 336 89

A patient with lung cancer treated by radiation and in remission presented with a two-month history of compulsive eating of raw, chilled potatoes. Suspicion of a pica due to iron-deficiency anemia was confirmed after complete laboratory evaluation. The source of iron loss was found to be gastrointestinal bleeding. Therapy with iron sulfate was begun, with a subsequent increase in the hemoglobin level; the pica ceased within one week of initiation of therapy. If searched for, pica is a common manifestation of iron deficiency; however, this patient apparently represents the first report of geomelophagia. Appropriate investigation of compulsive eating habits might lead to the diagnosis of iron deficiency and also allay patients' anxieties toward their behavior.
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PMID:Geomelophagia. An unusual pica in iron-deficiency anemia. 714 84

Iron-regulatory protein 2 (IRP2), a posttranscriptional regulator of iron metabolism, undergoes proteasomal degradation in iron-replete cells, while it is stabilized in iron deficiency or hypoxia. IRP2 also responds to nitric oxide (NO), as shown in various cell types exposed to pharmacological NO donors and in gamma interferon/lipopolysaccharide-stimulated macrophages. However, the diverse experimental systems have yielded conflicting results on whether NO activates or inhibits IRP2. We show here that a treatment of mouse B6 fibroblasts or human H1299 lung cancer cells with the NO-releasing drug S-nitroso-N-acetyl-penicillamine (SNAP) activates IRP2 expression. Moreover, the exposure of H1299 cells to SNAP leads to stabilization of hemagglutinin (HA)-tagged IRP2, with kinetics analogous to those elicited by the iron chelator desferrioxamine. Similar results were obtained with IRP2(Delta)(73), a mutant lacking a conserved, IRP2-specific proline- and cysteine-rich domain. Importantly, SNAP fails to stabilize HA-tagged p53, suggesting that under the above experimental conditions, NO does not impair the capacity of the proteasome for protein degradation. Finally, by employing a coculture system of B6 and H1299 cells expressing NO synthase II or IRP2-HA cDNAs, respectively, we demonstrate that NO generated in B6 cells stabilizes IRP2-HA in target H1299 cells by passive diffusion. Thus, biologically synthesized NO promotes IRP2 stabilization without compromising the overall proteasomal activity. These results are consistent with the idea that NO may negatively affect the labile iron pool and thereby trigger responses to iron deficiency.
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PMID:Nitric oxide inhibits the degradation of IRP2. 1568 86

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.
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PMID:Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer. 1930 38

Iron is a redox active metal involved in the oxidation-reduction reactions and regulation of cell growth and differentiation. Iron is an integral part of many proteins and enzymes that maintains various physiological functions. Most of the human body's iron is contained in red blood cells. Despite iron being an abundant trace metal in food, millions of people worldwide suffer from anemia. Iron deficiency results in impaired production of iron-containing proteins and inhibition of cell growth. In contrast, abnormal iron uptake has been related to the most common hereditary disease hemochromatosis, leading to tissue damage derived from free radical toxicity. In addition, disruption of iron regulation plays a key role in the etiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, Friedreich's ataxia and other neurological disorders, cancer (lung cancer, breast cancer, colon cancer), Fanconi anemia, stroke and ageing. Thus the control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease. The most frequent is the toxic role of iron linked with the catalytic decomposition of hydrogen peroxide (Fenton reaction) leading to the formation of reactive oxygen species (ROS) causing damage to biomolecules, including lipids, proteins and DNA. The binding of iron-designed chelators via nitrogen, oxygen or sulphur donor atoms blocks iron s ability to catalyze the formation of free radicals. Thus the design of various metal chelators to prevent free radical reactions is an important approach in the treatment of many iron-related diseases. The development of effective dual functioning antioxidants, possessing both metal-chelating and free radical-scavenging properties is awaited. The aim of this review is to discuss the role of iron and importance of iron-chelation in human disease and ageing.
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PMID:Importance of iron chelation in free radical-induced oxidative stress and human disease. 2190 63

Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.
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PMID:Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. 2766 97

Existing research yields conflicting results regarding the relation between iron deficiency and high serum ferritin (SF) levels in primary lung cancer patients. We investigated the concentrations of SF, hemoglobin (Hb) and transferrin (TRF) in 569 male primary lung cancer patients and 252 female primary lung cancer patients. We grouped the subjects according to gender, smoking status, menopausal status, pathological type, stage, and TNM stage. The levels of SF and TRF were correlated with T stage in male patients (p<0.01). The levels of SF and TRF were correlated with menopausal status in female patients (p<0.01). Hb was correlated with smoking status, pathological type, stage, and TNM stages in male patients(p<0.01), but in female patients, Hb was not correlated with these grouping factors(p>0.05). The levels of SF may be regulated by different mechanisms and may be of different physiological significance in different populations.
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PMID:Serum ferritin and primary lung cancer. 2919 Sep 45