Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite considerable progress in recent years in the understanding of the biology of multiple myeloma (MM), this disease remains incurable, although many new therapeutic approaches are under evaluation. The rapid development of recombinant technologies has permitted the production of large amounts of cytokines and growth factors, favoring the use of biotherapies also in this disease. Among these products, the interferons have been the most extensively used in clinical trials, giving the most promising results especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies, or to high dose chemotherapies followed by bone marrow (BM) or peripheral blood stem cell (PBSC) transplantation. However, more recently, a large number of cytokines and growth factors have been introduced in the clinical practice. Data of the use of erythropoietin have consistently demonstrated the role of this growth factor in ameliorating the grade of anemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Using hematopoietic growth factor in the mobilization of PBSC, the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of chemotherapy could be reduced. Despite the large amount of experimental data indicating a role for interleukins, as IL-2 and IL-6, in controlling tumor growth, there are only few clinical studies dealing with their use in MM. Results show that they arrest tumor progression rather than aid tumor regression, for this reason it appears that IL-2 and anti IL-6 antibodies should be investigated as maintenance therapy, in MM patients responding to chemotherapy. In the future it will be necessary to clarify for MM patients the role of other cytokines such as IL-1 beta and TNF alpha. A possible strategy to improve the clinical outcome of MM patients is to prevent the regrowth of residual tumor cells by establishing adoptive immunity at the stages of minimal residual disease previous obtained using chemotherapy. To this end a possible strategy is to induce an immune response against residual tumor cells by passive (using monoclonal antibodies) or active (using the idiotype expressed by malignant cells) immunotherapy.
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PMID:[The role of biotherapy in multiple myeloma]. 1107 35

The aim of this study was to examine the impact of anemia prevention by recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of cyclophosphamide in solid experimental tumors. Anemia was induced using a single dose of carboplatin (50 mg/kg i.v.) resulting in a long-lasting reduction (30%) of the hemoglobin concentration. In a second group, the development of anemia was prevented by rHuEPO (1000 IU/kg) administered s.c. three times/week starting 7 days before carboplatin application. Four days after carboplatin treatment, tumors (DS-sarcoma of the rat) were implanted s.c. onto the hind food dorsum. Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se. When tumors were treated with a single dose of cyclophosphamide (60 mg/kg i.p.) 5 days after implantation, a growth delay with a subsequent regrowth of the tumors was observed. In the anemia group, the growth delay was significantly shorter compared with nonanemic controls (13.3 days versus 8.6 days). In the group where anemia was prevented by rHuEPO treatment, growth delay was comparable with that of nonanemic controls (13.3 days). These results suggest that chemotherapy-induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas correction of anemia by rHuEPO treatment (epoetin alpha) increases the sensitivity, probably as a result of an improved oxygen supply to tumor tissue.
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PMID:Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors. 1124 34

The effect of malignant tumor growth on host's megakaryocytopoiesis and platelet production was studied in mice bearing transplantable Dalton's lymphoma. Tumor growth was paralleled by thrombocytosis, neutrophilia, and anemia. Platelet 51Cr half-life was normal but incorporation of 75Selenomethionine into circulating platelets was significantly enhanced in the tumor bearers suggesting stimulated thrombopoiesis while platelet life span remained unchanged. Megakaryocytes and their precursors, the small acetyl cholinesterase positive cells, were found in increased numbers in the bone marrow (BM) and particularly in the spleen where five to eight-fold rise was observed at the log phase of tumor growth. In addition, a remarkable increase in the number of megakaryocyte progenitors (CFU-MK and MK CFU-S) was observed both in the BM and spleen. Stimulation of these progenitors was more pronounced in the spleen than in the marrow, and the change was noticeable even from the third day of tumor bearing. Therefore, the results suggest that thrombocytosis associated with the growth of this experimental lymphoma was due to accelerated platelet production following stimulated megakaryocytopoiesis especially in the spleen.
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PMID:Stimulation of megakaryocytopoiesis and platelet production during growth of an experimental lymphoma. 1127 30

Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic features of these patients. Based on these observations, we evaluated the potential biological effects of rHuEpo on the course of tumor progression by using murine myeloma models (MOPC-315-IgAlambda(2) and 5T33 MM-IgG(2b)). Here we report that daily treatment of MOPC-315 tumor-bearing mice with rHuEpo for several weeks induced complete tumor regression in 30-60% of mice. All regressors that were rechallenged with tumor cells rejected tumor growth, and this resistance was tumor specific. The Epo-triggered therapeutic effect was shown to be attributed to a T cell-mediated mechanism. Serum Ig analysis indicated a reduction in MOPC-315 lambda light chain in regressor mice. Intradermal inoculation of 5T33 MM tumor cells followed by Epo treatment induced tumor regression in 60% of mice. The common clinical manifestation of myeloma bone disease in patients with multiple-myeloma was established in these myeloma models. Epo administration to these tumor-bearing mice markedly prolonged their survival and reduced mortality. Therefore, erythropoietin seems to act as an antitumor therapeutic agent in addition to its red blood cell-stimulating activity.
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PMID:Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. 1130 90

Fatigue is a common complaint of patients with cancer or other physical or mental disorders. In cancer patients, the estimated prevalence of fatigue is high (about 70% to 90% in different surveys). However, despite the high prevalence and widely recognized clinical relevance of fatigue, few studies have been performed to evaluate the putative causal factors and therapeutic approaches for this condition. The paucity of studies has been mainly because of the lack of proper instruments to quantify this clinical problem. Moreover, fatigue is multifactorial, which makes evaluation of precise relationships with other medical conditions difficult. In particular, fatigue is considered the cardinal symptom of anemia. The pathogenesis of anemia-related fatigue remains unclear, but some suggest that abnormalities in energy metabolism play a role in inducing fatigue. In cancer patients, this effect may be exacerbated by the increased metabolic needs associated with tumor growth. At the clinical level, the relationship between anemia and fatigue is universally accepted. However, early studies were unable to show a clear association between fatigue and hemoglobin levels. Recently, new insights were afforded by the implementation of innovative survey instruments that assess the effects of fatigue and other (nonfatigue) symptoms of anemia on the patient's well-being and quality of life. The use of these validated instruments has shown a direct effect of hemoglobin levels on fatigue and other quality of life parameters. Thus, amelioration of anemia and fatigue should be considered a primary endpoint of antineoplastic and supportive-care treatment of cancer patients. Accordingly, the search for new simplified methods of assessment of fatigue and other anemia-related symptoms and their treatment outcomes should be strongly encouraged.
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PMID:Fatigue: a main component of anemia symptomatology. 1139 47

The glycoprotein hormone erythropoietin is an essential viability and growth factor for the erythrocytic progenitors in the bone marrow. Tissue hypoxia is the main stimulus for the synthesis of the hormone in the kidneys and the liver. Endogenous erythropoietin and recombinant human erythropoietin (rHu-EPO) are similar with respect to their biological and chemical properties except for some microheterogeneities in their 4 carbohydrate chains. Generic products and alternatives to rHu-EPO are in development. Renal anemia can be corrected by rHu-EPO in a dose-dependent and predictable way without major side effects apart from a possible increase in arterial blood pressure. The optimal target hematocrit still needs to be defined. There are rare reports of antibody formation towards rHu-EPO in humans. Patients suffering from non-renal anemias may also benefit from the prescription of rHu-EPO. The drug has been approved for treatment of tumor patients with platinum-induced anemia. The cost-effectiveness and medical justification of the administration of rHu-EPO in tumor patients with respect to its positive effects on tumor oxygenation, tumor growth inhibition and support of chemo- and radiotherapy is still a matter of debate. In surgical patients, the pharmacological application of rHu-EPO can increase the yield of blood units in autologous blood donation programs and lower the severity and duration of postoperative anemia, if applicated some days prior to surgery. While rHu-EPO is a godsend in medical practice, its abuse as an performance enhancing drug by athletes in endurance sports is an unethical and potentially dangerous procedure. Unequivocal methods for detection of rHu-EPO doping still need to be established.
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PMID:Use of recombinant human erythropoietin as an antianemic and performance enhancing drug. 1146 58

This paper will present an overview of the evidence that links anemia with a poor prognosis in a variety of human tumors treated with radiation, surgery, chemotherapy or combinations thereof. Hypoxia, acute or chronic in type, is also associated with a poor prognosis, mediated through two possible routes: 1) resistance to therapy with radiation or chemotherapy, and 2) the development of a more "aggressive" tumor phenotype. While anemia and hypoxia are related to some degree in some patients, it is probable that not all of the associated negative impact of anemia is translated through the hypoxia pathway. Because of the clinical importance and essential role hypoxia plays in tumor growth and treatment response, hypoxia and anemia are possible key targets for new therapies. The identified downstream molecular events resulting in increased glycolysis, erythropoiesis and angiogenesis form specific pathways which offer targets for inhibition. The relationship between anemia and hypoxia is complex and not clearly understood. Their relationships and the mechanisms by which they impact on treatment outcomes require further extensive investigations in both the clinic and laboratory.
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PMID:[Effects of anemia and hypoxia on the course of tumors and the outcome of radiotherapy]. 1151 92

Fatigue is prominent in cancer patients and probably multifactorial in origin. Factors contributing to fatigue include anemia, weight loss, fever, pain, medication, and infection. In cancer patients, many of these factors are influenced by a frequently disrupted balance between endogenous cytokine levels and their natural antagonists. Indeed, cancer cells and the immune system appear to overexpress a range of cytokines in patients with malignancies. Some of these cytokines act as autocrine or paracrine growth factors for the neoplastic tissue while simultaneously causing secondary symptoms related to fatigue. For instance, cancer-associated anemia may be due to a blunted erythropoietin response and/or cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]), which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a hallmark of cancer, can be attributed to loss of appetite or enhanced energy expenditure. Several different interleukins, as well as TNF, interferon-gamma, and leukemia inhibitory factor, act as cachectins in animal models. Similarly, fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules that function as cytokine antagonists have been identified. These molecules may be exploitable in combating the components of cancer-related fatigue, and may inhibit tumor growth as well.
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PMID:The role of cytokines in cancer-related fatigue. 1159 87

Hypoxia induces tissue-specific gene products such as erythropoietin (EPO) and vascular endothelial growth factor (VEGF), which improve the peripheral O2 supply, and glucose transporters and glycolytic enzymes, which adapt cells to reduced O2 availability. EPO has been the fountainhead in research on pO2-dependent synthesis of proteins. The EPO gene enhancer (like the flanking DNA-elements of several other pO2-controlled genes) contains a consensus sequence (CGTG) that binds the trans-acting dimeric hypoxia-inducible factor 1 (HIF-1alpha/beta). The alpha-subunit of HIF-1 is rapidly degraded by the proteasome under normoxic conditions, but it is stabilized on occurrence of hypoxia. HIF-1 DNA-binding is also increased by insulin, and by interleukin-1 and tumor necrosis factor. Thus, in some aspects there is synergy in the cellular responses to hypoxia, glucose deficiency and inflammation. In viewing clinical medicine recombinant human EPO (rHu-EPO) has become the mainstay of treatment for renal anemia. Endogenous EPO and rHu-EPO are similar except for minor differences in the pattern of their 4 carbohydrate chains. RHu-EPO is also administered to patients suffering from non-renal anemias, such as in autoimmune diseases or malignancies. The correction of anemia in patients with solid tumors is not merely considered a palliative intervention. Hypoxia promotes tumor growth. However, the benefits of the administration of rHu-EPO to tumor patients with respect to its positive effects on tumor oxygenation, tumor growth inhibition and support of chemo- and radiotherapy is still debatable ground.
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PMID:Biology of erythropoietin. 1195 Jan 37

The major goal of this study was to examine the effects of total-body irradiation (TBI) on lung carcinoma progression and determine if changes in tumor growth could be correlated with radiation-induced alterations of immune system parameters. Lewis lung tumor cells were injected subcutaneously into syngeneic C57BL/6 mice that had been irradiated with a single 3.0 Gy dose of gamma-rays (60Co) at four time points either before or after tumor cell implantation. Subsequently, a second group of mice was irradiated 2 h prior to tumor injection with sequential doses of gamma-rays (0.46-2.66 Gy range). Assays were performed on blood and spleen from mice euthanized 16 days postimplantation. Tumor growth was consistently slower regardless of the timing of radiation exposure. However, dose of radiation influenced tumor growth delay. The preirradiated tumor-bearing mice had high CD4/CD8 T lymphocyte ratios along with increasing percentages of NKT cells in the blood supply with dose. Tumor-induced immunomodulation was also present, as evidenced by splenomegaly, low proliferative response to mitogens, and decreased spontaneous blastogenesis of leukocytes within the blood compared with normal values (P < or = 0.01). Anemia and thrombocytopenia were not observed with either tumor presence or irradiation. The present study demonstrates that a modest dose of TBI prior to tumor cell implantation resulted in a beneficial antitumor effect. A selective radiation-induced depletion of CD8+ T lymphocytes and changes in NKT cell percentages, correlated with findings from cytotoxicity assays, were indicative of a protumoricidal immune environment.
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PMID:Dose and timing of total-body irradiation mediate tumor progression and immunomodulation. 1220 76


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