Studies of the Anemia and Iron Metabolism in Cancer 1

Miller, Aaron; Chodos, Robert B.; Emerson, Charles P.; Ross, Joseph F.

doi:10.1172/jci103380

Cited by 89 publications

(18 citation statements)

References 26 publications

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“…The spleens of these animals synthesize both hemoglobin and ferritin at an increased rate. These results could explain the increased uptake of 59Fe by the spleen of tumorbearing mice, reported by Hevesy and Lockner (21), and may be applicable to the observations made in human malignancies of an anemia not associated with blood loss (22) and to the reports of an increased quantity of total iron in their spleens (23). The origin of spleen erythropoietic stimulation in animals bearing the tumor may be ascribed to hypoxia resulting from loss of bone marrow erythropoietic activity, or to a shortened life span of the circulating erythrocytes (21).…”

Section: Resultssupporting

confidence: 72%

Metabolism of the stimulated rat spleen

Mazur¹

1968

J. Clin. Invest.

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Section: Resultssupporting

confidence: 72%

Metabolism of the stimulated rat spleen

Mazur¹

1968

J. Clin. Invest.

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“…Failure of iron utilization has been described in these disorders (2,3), and studiesof mobilizable iron support this finding (4). A detailed understanding of the pathogenesis of the marrow failure is limited by incomplete knowledge about the normal development and function of the erythroid series and modification of these processes by disease.…”

Section: Introductionmentioning

confidence: 97%

Stimulation of globin synthesis: relative responsiveness of reticulocytes and nucleated erythroid cells

Waxman¹

1970

J. Clin. Invest.

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The effects of iron, cobalt, hemin, and plasma on hemoglobin synthesis by suspensions of rabbit reticulocytes and nucleated bone marrow cells were studied. L-Leucine-14C and sodium pyruvate-3-"C were employed to measure globin and heme synthesis, respectively. Normal plasma (or serum) was found to stimulate the rate of globin synthesis in both systems. The stimulatory effects of iron and hemin were additive to those of plasma or serum only in the reticulocytes.Cobaltous ion, at concentrations less than 1.0 mmole/ liter, was found to stimulate globin synthesis by reticulocytes as effectively as ferrous ion; cobalt was inhibitory only at concentrations greater than 3.0-5.0 mmoles/liter. Heme synthesis by reticulocytes was inhibited at all concentrations employed (0.2-5.0 mmoles/liter).In bone marrow nucleated erythroid cells, globin synthesis was markedly enhanced by exogenous hemin. In contrast to reticulocytes, however, bone marrow cells were unresponsive to either cobalt or transferrin-bound iron. Possible implications of these findings on regulation of the rate and mechanism of iron uptake and hemoglobin synthesis in vivo are discussed.

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“…Anemia commonly occurs in chronic infection, inflammation, and malignancy (1)(2)(3)(4). This anemia is characReceived for publication 14 June 1973 and in revised form 10 December 1973. terized by: (a) decreased plasma iron and iron-binding capacity; (b) impaired release of reticuloendothelial iron into the plasma; (c) modest decrease of red cell survival; and (d) relative failure of bone marrow to increase red cell production (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…This anemia is characReceived for publication 14 June 1973 and in revised form 10 December 1973. terized by: (a) decreased plasma iron and iron-binding capacity; (b) impaired release of reticuloendothelial iron into the plasma; (c) modest decrease of red cell survival; and (d) relative failure of bone marrow to increase red cell production (1)(2)(3)(4)(5)(6)(7). These clinical similarities have resulted in the classification of these anemias in a single category, the anemia of chronic disorders (ACD)1 (8).…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Erythropoiesis in the Anemia of Infection, Inflammation, and Malignancy

Zucker¹,

Friedman²,

Lysik³

1974

J. Clin. Invest.

102

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A B S T R A C T A major factor in the anemia of infection, inflammation, and malignancy is a relative failure of the bone marrow to increase erythropoiesis in response to a shortened red cell survival. The possible causes for this diminished marrow response are: (a) a reduced production of erythropoietin, or, (b) impaired bone marrow response to erythropoietin. In this report studies were performed on 6 normals, 13 patients with anemia from infection or inflammation, and 18 patients with anemia caused by advanced malignancy. Serum erythropoietin activity was measured using the posthypoxic, polycythemic mouse assay. Assessment of bone marrow response to erythropoietin was made by measuring '9Fe-heme synthesis in bone marrow suspensions cultured for 3 days with and without the addition of erythropoietin. The results showed that marrow heme synthesis was increased in erythropoietin-treated cultures as compared with saline control cultures by 66± 8% (mean +SE) in normals, 101±10% in patients with infection or inflammation, and 31±5% in malignancy.Serum erythropoietin levels were consistently diminished relative to expected levels for the degree of anemia in the infection-inflammatory group, but not in malignancy.In these patients, plasma inhibitors to the biological activity of erythropoietin were not detected in vitro.These studies suggest that another factor to consider in the anemia of malignancy is a decreased bone marrow response to erythropoietin. In the anemia of infectioninflammation, marrow response to erythropoietin is normal, but serum levels of erythropoietin are decreased relative to the degree of anemia.

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Studies of the Anemia and Iron Metabolism in Cancer 1

Cited by 89 publications

References 26 publications

Metabolism of the stimulated rat spleen

Metabolism of the stimulated rat spleen

Stimulation of globin synthesis: relative responsiveness of reticulocytes and nucleated erythroid cells

Bone Marrow Erythropoiesis in the Anemia of Infection, Inflammation, and Malignancy

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