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EN
Introduction: Expression of Epo, a glycoprotein secreted by the fetal liver and the adult kidney in response to cellular hypoxia and its receptor have been described in human solid tumors, such as colon and breast cancer. Purpose: Since activation of Epo-EpoR signaling pathway in erythroid progenitor and precursor cells leads to promotion of proliferation and differentiation or prevention of programmed cell death through Bcl-xl and Bcl-2 it was of interest to investigate expression of Epo, EpoR, apoptosis regulator – Bax and marker of proliferating cells - Ki-67 and assess correlation between them, with regard to clinicopathological variables of colorectal cancer. Materials and methods: The correlations between expression of Epo, EpoR, Bax and Ki-67 in colorectal cancer were analyzed in regard to patient age, sex, primary localization, histopathological type, grading, staging and lymph node invasion. Statistical analyses were performed by using the Spearman rank correlation test applying a significance level of p<0,05. Results: Correlation between Bax and EpoR is positive and statistically significant at all groups of patients except group pT1+pT2. Positive correlation between Bax and Epo is statistically significant at following groups of patients: all patients, age  60, age >60, male, female , primary localization in rectum, primary localization in colon, adenocarcinoma, G2, G3. Statistical analysis revealed no significant correlations between expression of neither Ki-67 with Epo nor Ki-67 with EpoR in all groups of patients. Conclusions: Epo seems to be a pleiotropic cytokine, which can exert its biological effect on several cell types, including neoplastic cells. The effect of Epo-EpoR signaling can differ in various cells and conditions.
EN
Anaemia is one of the most frequently diagnosed complications in cancer patients and also occurs during the course of cancer treatment. The condition can be observed in as many as 60–70% of patients who receive chemotherapy or radiotherapy. As a cancer symptom, it is found in 30% of cases and is particularly severe when accompanied by kidney failure. In patients undergoing cancer therapy, anaemia is treated with PRBC transfusions and/or recombinant human erythropoietin. The article discusses 3 case studies of patients with late-stage cancer (pleural mesothelioma, urothelial kidney carcinoma, and lung carcinoma), who suffered from moderate to severe anaemia during aggressive treatment with chemo- and radiotherapy. All 3 patients were treated with erythropoietin, which made it possible for them to stay on chemotherapy and/or undergo radiotherapy. Thanks to erythropoietin, they did not require PRBC transfusions and their general condition and quality of life improved. They tolerated the treatment well and no complications were observed.
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EN
In recent years anaemia has been recognized as one of the most specific and evident manifestations of chronic renal failure. In the majority of cases, renal anaemia is normocytic and normochromic with normal cellularity of bone marrow. Multiple factors contribute to the molecular origins of the anaemia of chronic kidney disease. Within those factors, the disturbances in the production of erythropoietin have the greatest impact on the disease pathogenesis. However, other components such as shortened erythrocyte survival, blood loss, iron or other nutritional deficiencies, hemolysis, the presence of uremic inhibitors of erythropoiesis among others can also significantly contribute to the occurrence of anaemia.
EN
A possibility of recognition of the clinical status of patients with amyotrophic lateral sclerosis (ALS) in relation to severity of the disease was investigated. Three groups: (i) healthy controls (n=15) and two subgroups of ALS patients (ii) mild (n=15) and (iii) severe (n=15) were considered as classes. Four features of the subjects: (i) their age (AGE) (ii) erythropoietin concentration in serum (SERUM), (iii) in cerebrospinal fluid (CSF), and (iv) duration time of the disease (Tdis) were used for classifier construction based on the k Nearest Neighbours (k-NN) rule, known from pattern recognition theory. The presented results demonstrate that the pattern recognition approach may be useful for the evaluation of the severity of the ALS disease.
EN
Erythropoietin is a potent regulator of erythropoiesis. It acts via the specific membrane receptor (EpoR). Erythropoietin is also known to be present in the central nervous system, and its concentration and the expression of EpoR change during development, which raises the possibility that this modulator might be involved in the regulation of neuronal functions in the developing brain. The GABAergic system undergoes profound changes during development and is particularly susceptible to modulation by endogenous factors. Therefore, we decided to investigate the impact of Epo on GABAergic transmission in hippocampal neurons developing in vitro. An analysis of miniature IPSCs (mIPSCs) revealed that a long-term treatment with Epo (48 or 72 h) resulted in a major acceleration of the decaying phase of these currents while the amplitude and current frequency remained unchanged. Interestingly, this effect was restricted to the youngest considered age group (6-8 DIV), indicating that Epomediated modulation of mIPSCs depends on the developmental stage of the neurons. We conclude that Epo may exert a modulatory action on GABAergic transmission in developing neural networks.
EN
Preclinical studies conducted over the past 10 years have shown that EPO is not only a hormone that regulates erythropoiesis, a major growth factor, but also a cytoplasm with pleiotropic activity that also affects cancer cells. The expression of EPO and its receptor (EPOR) occurs in many cancers of various origins. The EPO/EPOR system is active in many cancer cells and is involved in the modification of molecular signaling pathways and the stimulation of growth, survival, motility and the ability to create metastases. EPO can also increase the resistance of cancer cells in vitro and in vivo to chemotherapy and radiotherapy.
EN
Platelet production increases in anemic people. In particular, iron deficiency causes reactive thrombocytosis in such patients. Although anemia and iron deficiency are frequently seen in dogs, there are no published studies on this subject. The aim of the present study was to investigate the relationship between anemia, iron deficiency, and platelet production in dogs. A total of 81 dogs brought to the university animal hospital with signs of anemia were used. Haemogram parameters, serum iron (Fe), erythropoietin (EPO), and thrombopoietin (TPO) levels, as well as total iron binding capacity (TIBC), were measured. Transferrin saturation (TSAT) ratios were calculated. The animals were categorized as anemic or non-anemic, mildly anemic or moderately/ severely anemic, and having iron deficiency or no iron deficiency according to haemogram parameters and the serum Fe level. A high platelet number was observed in dogs with mild anemia. Dogs with mild anemia also had higher serum EPO levels than dogs with moderate/severe anemia (P = 0.047). Iron deficiency was detected in 31 dogs. The platelet number was higher in dogs with iron deficiency (P = 0.004). It was also observed that dogs with iron deficiency had higher serum EPO levels (P = 0.027) and lower TPO levels (P = 0.025) than dogs without iron deficiency. In conclusion, it can be said that mild anemia and iron deficiency cause thrombocytosis in dogs. The increased serum EPO levels, both in dogs with mild anemia and those with iron deficiency, suggest that the increase in platelet production is due to EPO. Nevertheless, there is a need for further research to fully understand the underlying mechanism.
EN
Erythropoietin (EPO) has a beneficial effect on hepatic cell proliferation during liver regeneration. However, the underlying mechanism has not yet been elucidated. To uncover the proliferation response of EPO in rat liver regeneration after partial hepatectomy (PH) at the cellular level, hepatocytes (HCs) were isolated using Percoll density gradient centrifugation. The genes of the EPO-mediated signaling pathway and the target genes of the transcription factor (TF) in the pathway were identified in a pathway and TF database search. Their expression profiles were then detected using Rat Genome 230 2.0 Microarray. The results indicated that the EPO-mediated signaling pathway is involved in 19 paths and that 124 genes participate, of which 32 showed significant changes and could be identified as liver regeneration-related genes. In addition, 443 targets regulated by the TFs of the pathway and 60 genes associated with cell proliferation were contained in the array. Subsequently, the synergetic effect of these genes in liver regeneration was analyzed using the E(t) mathematical model based on their expression profiles. The results demonstrated that the E(t) values of paths 3, 8, 12 and 14–17 were significantly strengthened in the progressing phase of liver regeneration through the RAS/MEK/ERK or PI3K/AκT pathways. The synergetic effect of the target genes, in parallel with target-related cell proliferation, was also enhanced 12–72 h after PH, suggesting a potential positive effect of EPO on HC proliferation during rat liver regeneration. These data imply that the EPO receptor may allow EPO to promote HC proliferation through paths 3, 8, 12 and 14–17, mediating the RAS/MEK/ERK and PI3K/AκT pathways in rat liver regeneration after PH.
EN
Pre-operative treatment with recombinant human erythropoietin may improve aortic stenosis patients' condition, including anemia and/or cardiac dysfunction, for subjecting to aortic valve replacement. In this study, we tested this hypothesis in a mouse model of aortic stenosis. Adult male mice were subjected to either aortic stenosis created by aortic ligature or sham operation. Aortic stenosis for 4 weeks caused cardiac hypertrophy, pulmonary congestion and left ventricular dysfunction. It was associated with increased levels of tumor necrosis factor-a in serum and myocardium, and reduced levels of interleukin-10 in myocardium but not in serum. Mytocyte apoptosis rate, level of cleaved caspase 3, activity of nuclear factor-B and expression of p38-MAPK pathway were also elevated. Erythropoietin treatment increased hematocrit but did not prevent the development of cardiac hypertrophy. It, however, reduced the apoptosis, prevented the increases in tumor necrosis factor-, nuclear factor-B activation and phosphorylation of p38, and attenuated the increases in lung weight, the decreases in LVEF and LVFS, and the increases in LVDd and LVDs. In conclusion recombinant human erythropoietin has cardioprotective effects in maladaptive cardiac hypertrophy by inhibiting nuclear factor-B activation, phosphorylation of p38-MAPK pathway, and production of tumor necrosis factor-, together leading to a reduced apoptosis.
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