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)

Acute Trypanosoma congolense infection induced moderate, transient anemia in N'Dama cattle (trypanotolerant) and severe anemia in Boran cattle (trypanosusceptible). Erythropoietin receptor (EpoR) was cloned and sequenced from the two breeds of cattle. A single position mutation of Tyr in the Boran to His in the N'Dama predicted amino acid sequence was revealed. The mRNA transcription of erythropoietin (Epo) in kidneys and EpoR in the bone marrow of infected cattle was determined by competitive reverse transcription and the polymerase chain reaction (RT-PCR). Though Epo mRNA transcription increased in the kidneys during infection, the increase was not significantly different (p>0.05) between the two breeds of infected cattle. The level of EpoR transcripts in the bone marrow of infected N'Damas was significantly higher (p<0.05) than that detected in the marrows from infected Boran cattle. While infection seem to increase levels of transcription of IL-1alpha and beta, and TNFalpha in kidneys from both Boran and N'Dama cattle, no significant difference was detected in the level of mRNAs of these cytokines in the kidney from the two breed of cattle. The amount of IFNgamma mRNA transcripts were not changed with infection in N'Dama cattle, while on the contrary a significant higher levels of IFNgamma was found in kidneys from infected Boran cattle as compared to the other groups. A significant (p<0.05) increase in the levels of IL-1alpha and beta, and IFNgamma mRNA transcripts were detected in the marrows of infected Borans as compared to the infected N'Dama cattle. In this study the increase in the level of TNFalpha mRNA in the marrows of the two infected breeds was not different. This implies there is no negative effect of TNFalpha on hematopoiesis during acute infection. These findings suggest that the levels of Epo and EpoR in the infected Boran cattle were inadequate for their degree of anemia, which might be due in part to high expression of IFNgamma during acute infection with T. congolense.
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PMID:Analysis of erythropoietin and erythropoietin receptor genes expression in cattle during acute infection with Trypanosoma congolense. 992 42

Erythropoietin (EPO) is the primary regulator of erythropoiesis, and promotes the survival, proliferation, and differentiation of erythroid progenitor cells. The EPO receptor belongs to the same family of receptors as growth hormone, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, and some interleukins. In the erythropoietic process, EPO induces homodimerization of the EPO receptor, which is located on the surface of erythroid progenitor cells. Dimerization activates the receptor-associated Janus kinase 2 via transphosphorylation. Specific tyrosines in the intracellular portion of the receptor are phosphorylated and serve as a docking site for intracellular proteins, including one of the signal transducers and activators of transcription (STAT5). This results in activating various cascades of signal transduction. STAT5 enters the nucleus on phosphorylation, inducing the transcription of erythroid genes. Phosphatases dephosphorylate Janus kinase 2 and downregulate the EPO receptor. Erythropoietin receptor activation seems to exert its effect by inhibiting apoptosis rather than by affecting the commitment of erythroid lineage, although the mechanism by which this occurs is as yet unclear. Anemia in cancer is associated with excessive production of cytokines that inhibit EPO synthesis, thereby interfering with the normal erythropoietic process, which leads to a reduction in red blood cells and the ability to oxygenate tissue.
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PMID:The erythropoietin receptor. 1139 48

Erythropoietin receptor (EpoR) has been reported to be overexpressed in tumours and has raised safety concerns regarding the use of erythropoiesis-stimulating agents (ESAs) to treat anaemia in cancer patients. To investigate the potential for EpoR to be overexpressed in tumours, we have evaluated human tumours for amplification of the EPOR locus, levels of EPOR transcripts, and expression of surface EpoR protein. Gene amplification analysis of 1083 solid tumours found that amplification of the EPOR locus was rare with frequencies similar to other non-oncogenes. EPOR transcript levels in tumours and tumour cell lines were low in comparison with bone marrow and were equivalent to, or lower than, levels in normal tissues of tumour origin. Although EpoR mRNA was detected in some tumour lines, no EpoR could be detected on the cell surface using (125)I-Epo binding studies. This may be due to the lack of EpoR protein expression or lack of cell-surface-trafficking factors, such as Jak2. Taken together, we have found no evidence that EpoR is overexpressed in tumours or gets to the surface of tumour cells. This suggests that there is no selective advantage for tumours to overexpress EpoR and questions the functional relevance of EpoR gene transcription in tumours.
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PMID:Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells. 1834 18

Erythropoiesis-stimulating agents (ESA) used for the treatment of chemotherapy-induced anemia in cancer patients have been associated with adverse outcomes of enhanced tumor progression and impaired survival in a series of recent clinical trials. As clinical practice guidelines for ESA administration in cancer patients have evolved to improve safety, the mechanisms underlying the adverse outcomes and whether ESAs exert direct and/or indirect effects in primary tumors to modulate tumor cell growth, survival, and chemoradiotherapy responses remain uncertain. Erythropoietin receptor (EpoR) expression in tumor cells has raised the simplistic possibility that Epo signaling mediated via a functional cellular receptor may contribute to tumor progression in a direct manner. However, Epo biology in cancer is likely to be complex and an interplay of multiple factors is potentially involved in the overall tumor response to exogenous Epo. Optimization of ESA use as an important supportive therapy modality in cancer patients, and further investigation of the role of Epo-EpoR in cancer biology will require a combination of carefully designed preclinical and clinical studies designed to ascertain not only the effect of ESA therapy on clinical outcomes such as tumor response, progression-free, and overall survival but also to investigate the potential effects of Epo on biomarkers of EpoR activation and factors related to tumor biology and chemoradiation responsiveness.
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PMID:Erythropoiesis-stimulating agent use in cancer: preclinical and clinical perspectives. 1867 35