Background . Colorectal cancer is the most commonly diagnosed cancer among all malignant neoplasms. This disease is accompanied by the development of anemic syndrome (AS). This complication not only worsens the results of treatment and, as a result, reduces overall survival, but also reduces the quality of life of patients, reduces adherence to treatment. Aim . To study the expression of hepcidin 25 (HP25), prohepcidin (PROHP), ferritin (FR), interleukin 6 (IL-6) and metabolites of nitric oxide (NO x ) in the peripheral blood of patients colorectal cancer, to assess their relationship with the clinical course of the disease and with AS. Materials and methods . The study was conducted in 41 patients with colorectal cancer and AS. The content of FR, PROHP, HP25, IL-6 was determined using enzyme immunoassay. The total content of NOx in blood serum was determined using the Griess reagent after the reduction of nitrate to nitrite with cadmium granules in the presence of zinc. Results . There are three types of AS. A characteristic feature of which was microcytosis (MCV – 74.3 ± 2.1 fl) and hypochromia (MHC – 22.9 ± 1.2 pg) of erythrocytes. Type 1 of AS – iron deficiency anemia (IDA), type 2 – anemia of chronic diseases (ACD) in combination with iron deficiency erythropoiesis and type 3 – ACD with functional iron deficiency (FID). True IDA was detected in 15 (36.6 %) patients, which was classically characterized by: low concentration of FR, PROGP, GP25, IL-6 and NO x . A less significant group (9 patients, 21.9 %) had a high concentration of FR and low PROHP, GP25, IL-6, NO x , which indicated iron deficiency against the background of ACD. It differed from the first group with IDA in a significant concentration of FR, which may indicate the transition of IDA to the chronic phase of AS. Third group (17 patients, 41.5 %) – with FID – turned out to be the most numerous and characterized by a high concentration of FR (386.7 ± 41.2 ng/ml), GP25 (43.2 ± 7.1 ng/ml), PROHP (283.3 ± 18.5 ng/ml), IL-6 (24.8 ± 5.5 pg/ml), NOx (39.7 ± 5.5 µmol/l), the values were significantly higher (p <0.001) than in patients with IDA and ACD with iron deficiency erythropoiesis. Conclusion . In patients with a widespread tumor process, AS with FID is most often detected. FID was accompanied by hyperproduction of FR, IL-6, GP25, PROGP and NO x . A close correlation was noted between the studied parameters with an increase in the T-stage of colorectal cancer. This may indicate the relationship of these proteins in the development of cytokine-induced anemia in cancer patients. The data obtained can be widely used to assess the state of metabolic disorders in anemia associated with malignant neoplasms for the differential diagnosis of AS variants and adequate treatment.
Introduction. Anemia syndrome is a common disease that reduces the quality and life expectancy of cancer patients. Prevention, timely diagnosis and effective treatment of anemia are statistically significantly associated with a favorable clinical outcome of the treatment of patients, and also contributes to better tolerability of anticancer therapy.Aim. Evaluation of the effectiveness of oral iron preparations and parenteral use of erythropoietin-alpha in patients with breast cancer and colorectal cancer, iron deficiency anemia or severe iron deficiency, immediate and long-term results of treatment, as well as the quality of life of patients with breast cancer and colorectal cancer.Materials and methods. A retrospective analysis of the material from the Blokhin National Medical Research Center of Oncology, involved 133 patients (validation group 68 people, control group – 65 people), patients with breast cancer or colorectal cancer, suffering from anemia. Depending on the form of anemia, patients were prescribed therapy – oral iron preparations with epoetin alfa in combination or in monotherapy. The effectiveness of therapy was assessed by the rate of blood hemoglobin. Analysis and statistical processing of results using IBM SPSS Statistics 26.0. Survival analysis was carried out using the KaplanMeier method. Descriptive statistics methods are used to analyze socio-demographic and traditional patients.Results. With a median follow-up of 61.2 months, the exclusion groups did not have significant differences in overall survival (p > 0.05). However, the group of patients with IDA who received therapy to correct the anemic syndrome and the group with FDA without adequate therapy had a greater significance in terms of 5-year OS (93.5 and 69.6%, respectively; p = 0.02). There were also no significant values for the 5-year DFS indicator (p > 0.05). However, the groups of patients with IDA who received and did not receive therapy to correct anemia probably made a big difference in terms of 5-year DFS (90.3 and 63.9%, respectively; p = 0.025). The group of patients with IDA treated with anemia to correct anemic syndrome clearly differed from the group of patients with FAD without therapy to correct anemia in terms of 5-year OS (90.3 and 43.6%, respectively; p < 0.001).Conclusions. Carrying out antianemic therapy can significantly increase the 5-year relapse-free survival in patients with iron deficiency anemia (90.3 and 63.9%, with and without therapy, respectively; p = 0.025).
Background. The pathways of iron acquisition, outflow, storage and regulation are disrupted in cancer, which suggests that the reprogramming of iron metabolism is one of the central aspects of the survival of tumor cells.Aim. Is to review and generalize modern literature data on the regulation of hepcidin, ferroportin and prospects for the correction of iron metabolism in cancer patients.Materials and Methods. The paper presents the results of international and domestic studies of the peculiarities of iron metabolism and the prospects for its correction in cancer patients. The search for relevant sources was carried out in the web of Science, PubMed, Medline, eLibrary.ru systems for 1988–2023. Of the analyzed studies 61, the most relevant, were used to write a systematic review.Results. Over the past decade, a new understanding has emerged of the role of proteins, in particular hepcidin and ferroportin, which regulate cellular iron in cancer growth, angiogenesis and metastasis. New treatment methods with hepcidin-modifying strategies and stabilizers of hypoxia-induced factors are emerging, but their therapeutic efficacy for correcting iron metabolism in cancer patients needs to be evaluated and clinical trials.Conclusion. Analysis of the literature data has shown the high relevance of studies of the regulation of hepcidin and ferroportin in cancer patients and the need for further study of this problem.
Early and adequate correction of the anemic syndrome (AS) of cancer patients can prevent deterioration in the quality of life and be considered as a reserve for increasing the effectiveness of treatment for breast cancer (BC). The aim of the study was to assess the status of iron using modern methods of ferrokinetics in breast cancer patients on the background of adjuvant chemotherapy for early diagnosis and adequate treatment of AS. The object of the study included 21 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, against the background of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25); ferritin (FR); soluble transferrin receptors (rRTP); transferin (TRF); iron (Fe); erythropoietin (EPO); CRP and IL-6 indicators. AC correction was performed (ferinject, epotin-alpha, B12). 10 (47.6%) patients with breast cancer had AS. Most of them were diagnosed with IDA with microcytic, hypochromic characteristics of erythrocytes, low concentration of FR, Fe, GP25, IL-6, CRP, and high levels of TRP and rRTP. Functional iron deficiency (FDF) was established in some patients. In contrast to patients with IDA, they had a high concentration of FR, CRP and significant production of GP25, IL-6. The EPO level was not optimal for the majority of patients with AS. In isolated cases, during treatment with recombinant erythropoietins, a deficiency of vitamin B12 (cyanocobalamin) was revealed. The rational use of iron preparations, vitamins, and recombinant forms of EPO made it possible to restore Fe metabolism, stabilize the hemoglobin level, and also improve the condition of most breast cancer patients. The obtained data on IL-6, GP25, CRP indicate a certain relationship between them in the development of anemia with VDF in breast cancer patients and the need for further study of the characteristics of iron metabolism in cancer patients.
Introduction. Numerous studies using multivariate analysis have confirmed the relationship between low hemoglobin and / or hypoxia of tumor tissue with a worsening prognosis.The study objective was to assess the state of iron metabolism in breast cancer patients in the perioperative period, before conducting adjuvant chemotherapy for adequate administration of iron and recombinant erythropoietins preparations.Materials and methods. The object of the study included 17 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, before the first course of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25), ferritin, soluble transferrin receptors, transferin, iron, erythropoietin, C-reactive protein and interleukin 6 indicators.Results. In patients with breast cancer, even before adjuvant chemotherapy, a violation of iron metabolism was revealed. Anemic syndrome (AS) with iron deficiency erythroproiesis was diagnosed in 29.4 % of them. In most of them, AS was accompanied by a deficiency of endogenous erythropoietin. Iron deficiency anemia was more common; functional iron deficiency (FID) was found in some patients. In contrast to patients with iron deficiency anemia, patients with FID had a significant concentrations of GP25, C-reactive protein, and interleukin 6 and ferritin were within the upper limit of normal. It should be noted that GP25 hyperexression was observed not only in breast cancer patients with FID, but also in patients without laboratory signs of anemia, which did not exclude the latent stage of AS.Conclusion. To achieve the effectiveness of the treatment of AS, a comprehensive and personalized approach is required. Iron preparations are prescribed to restore iron metabolism; recombinant erythropoietins preparations are used to increase the rate of erythrocyte formation during chemotherapy. The same treatment regimen is justified for the correction of AS with FID. However, the strategy for future treatment of FID is associated with the use of GP25 antagonists (in order to overcome the retention of iron in the reticuloendothelial system), hormones or cytokines that can effectively stimulate erythropoiesis in AS with impaired iron metabolism.
The study was performed in 9 cancer patients with sepsis. A clinical blood test of patients with sepsis was accompanied by a neutrophilic leukemoid reaction, with the appearance in the differential count of white blood cells of young cells (myelocytes, metamyelocytes). According to the literature, it is shown that in severe sepsis, a local infection is accompanied by systemic of neutrophil activation (NF). Moreover, excessive activation and location of NF in the microvasculature, especially its young forms and the formation of extracellular trap networks (NETs), can contribute to pathological manifestations of multiple organ failure and thrombosis.
In the blood serum of 93 patients with various localities of the malignant process, the content of nitric oxide (NO), indicators of lipid peroxidation (POL): superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione in red blood cells were determined. 9 patients with ovarian cancer were examined during chemotherapy (6 courses), 40 patients with colon cancer, previously operated, were with malignant liver damage. In 39 patients with anemia, NO indicators were compared with the level of interleukin 6 (IL-6) and hepcidin-25 (GP-25). As a control, 60 practically healthy individuals were examined. It was shown that the NO content was significantly reduced in 69.7% of patients, regardless of the location of the primary tumor. There was a gradual increase in the NO content before each course of chemotherapy. A high concentration of NO (more than 22 µM) was detected in 22 patients with functional iron deficiency (FJ) against the background of anemia of chronic diseases (AHZ), which was accompanied by hyperexpression of IL-6 (27.0±10.5 pg/ml) and GP-25 (25.2±7.1 ng/ml). In contrast, the lowest NO values (less than 22 µM) were observed in 17 patients with IDA. There is no doubt that there is a certain relationship between the development of oxidative stress with the accumulation of highly toxic lipoperoxidation products that affect the overall homeostasis of the body, and the development of anemic syndrome.
Introduction. In recent years, a separate publications have appeared indicating that interleukin 6 (IL-6) and the protein hepcidin 25 (GP25) play a significant role for the development of functional iron deficiency (FID) in oncological patients with a widespread tumor process. It is important to differentiate between FID and iron deficiency anemia (IDA), since they have the same morphological characteristics, but their treatment is fundamentally different.The aim of this study was to study the main metabolites of ferrokinetics, IL-6 and C-reactive protein (CRP) expression parameters in patients with breast cancer on the background of neoadjuvant chemotherapy to develop individual approaches to the diagnosis and treatment of anemic syndrome (AS), prediction, early detection of anemia and its adequate correction.Materials and methods. The study was conducted in 31 breast cancer patients, during of 6 cycles of chemotherapy. The main metabolites of ferrokinetics were studied: GP25, ferritin, soluble transferrin receptors, transferrin, iron, erythropoietin, IL-6 and CRP indices. The control group consisted of 29 apparently healthy women.Results. AS was detected in 14 (45.1 %) of breast cancer patients. IDA prevailed with microcytic, hypochromic characteristics of erythrocytes, a low concentration of ferritin, iron, GP25, IL-6, CRP, and a high level of transferrin and soluble transferrin receptors. A some patients were diagnosed with FID, mainly with the III and IV stages of the disease. Unlike IDA, they had a high concentration of ferritin, CRP and significant production of GP25, IL-6. Erythropoietin level was not optimal for the majority of patients with AS. A few patients on the background of treatment with recombinant erythropoietins revealed a deficiency of vitamins B12 (cyanocobalamin) and folic acid.Conclusion. Early diagnosis, a personalized approach to the prescription of iron preparations, recombinant erythropoietins, vitamins B12 and folic acid in patients with AS allowed for 6 cycles neoadjuvant chemotherapy without a significant decrease in erythrocytes, hemoglobin and hematocrit in most of them. The data obtained on IL-6, GP25, and CRP indicate relationship between them in the development of FID in breast cancer patients with a widespread tumor process and require further study.
The purpose of the study was a systemic literature review on data regarding the efficacy, safety and prospects for the use of adjuvant chemotherapy for locally advanced gastric cancer.Material and Methods. The study contained a thorough literary analysis of the results of international studies on the use of preoperative and postoperative chemotherapy for locally advanced gastric cancer. Relevant sources were searched in Medlin and Cochrane Library databases, and publications from 2001 to 2019 were included. Of all the studies analyzed, 28 were used to write the systematic review.Results. The increase in survival rates was mainly achieved due to the use of a multimodal approach to the treatment of gastric cancer. The effectiveness of this approach, which combined surgery with chemotherapy or chemoradiotherapy, was proven in several large clinical studies. However, despite the large number of treatment options for locally advanced gastric cancer, there is still no single standard for the management of patients with this disease. One of the treatment options successfully practiced in a number of leading countries is the use of adjuvant chemo/chemoradiation therapy.Conclusion. Analysis of the literature data of the last 18 years has shown the high relevance of studies on adjuvant chemotherapy for gastric cancer and the need to continue further study of this problem.
A study of interleukin-6 (IL-6), hepcidin-25 (GP-25) was conducted in 22 patients with breast cancer before neoadjuvant chemotherapy and in 27 healthy women in the control group. Significant expression of the GP-25 protein was revealed in breast cancer patients, compared to control. The rates were high both in patients with anemic sindrome (AS) and without it (p <0.01). Latent iron deficiency, AS, IDA and functional iron deficiency (FJ) were more often detected in patients with stage III disease. A significant difference in the parameters of GP-25 and IL-6 was noted, the indicators were higher in patients with stage III (p <0.01). No close correlation was found between IL-6, GP-25 and other acute-phase proteins (FR, CRP) at the initial stages of AS formation. On the contrary, a positive correlation was observed in patients with IDA and FJ between IL-6 and all acute-phase proteins (GP-25, FR, CRP). However, a small number of observations do not allow an unambiguous conclusion about the role of IL-6 and GP-25 expression in the development of AS in cancer patients with breast cancer and requires further study.
A study of the main indicators of red blood (RBC, HGB, HCT, MCV, MCH) and the concentration of EPO, sTfR in 9 cancer patients with anemic syndrome (AS) against sepsis was carried out. Among them, patients with chronic disease anemia (ACh), with normocytic, normochromic characteristics of red blood cells and low hematocrit predominated. In 2 patients, microcytosis and erythrocyte hypochromia were noted, the concentration of sTfR was significantly higher than normal (0.9 ± 0.07 μg / ml), amounted to 2.7 μg / ml in one of them and 1.9 μg / ml in the other, which testified to t iron deficiency erythropoiesis (IDE) on the background of the ACh,. In 7 patients with ACh without IDE, sTfR values were within the normal range (0.1-1.2) μg / ml, the median was 0.5 μg/ml. In all patients with sepsis, the production of EPO was inadequate for the severity of the AS, to a lesser extent in patients with IDE. The average EPO production in the group was 19.4 ± 5.1 (7.7-52.8) mU / ml, median = 12.1 mE / ml. Further studies of EPO, sTfR are planned in order to determine their role in therapeutic tactics in the correction of AS in cancer patients with sepsis.
Anemic syndrome (АС) is a frequent complication of cancer that gives poor results of treatment and reduces quality of live of patients. The literature review is devoted to the role of the peptide hormone hepcidin 25 (HP25), which regulates systemic and local iron homeostasis, in the development of anemia. The main biological function of HP25 is to reduce the level of iron in the bloodstream, which realizes a decrease of the mobilization of iron from the depot and a decrease of absorption of iron in the intestine. Modern approaches to the diagnosis and treatment of anemic disease in oncological practise necessarily include an assessment of the level of HP25. It was shown that HP25 is involved in the pathogenesis of anemia in malignant neoplasms. Oncological diseases are often accompanied by high levels of pro-inflammatory cytokines, in particular interleukin-6 (IL-6), which causes an increase in the production of HP25. Under the influence of IL-6, HP25 blocks ferroportins and iron release by macrophages, which leads to the development of functional iron deficiency and iron deficiency erythropoiesis, thus, with prolonged exposure to pro-inflammatory cytokines, anemia of chronic disease develops. The treatment of АС associated with malignant neoplasms is a complex procedure. Therapeutic effect on HP25 and IL-6 is a promising prospect for the correction of anemia in cancer patients. New strategies in the pathogenetic therapy of patients with anemia are associated with the use of antihepcidin drugs that reduce the level of HP25 in the blood. However, some studies have shown that an increase in the iron content in the bloodstream increases its accessibility to the tumor and promotes its growth; therefore, further, more in-depth study of the problem of correcting АС in cancer patients is necessary
Abstract The influence of digital noise of the optical range sensor on the characteristics of microscopic objects of study was experimentally evaluated. A reference sample of smears, from which images of medical objects of research were obtained, was formed for the research. Blood cells were used as such objects. As a result of research textural signs are calculated and the analysis of their change is carried out. The obtained estimates allow to draw preliminary conclusions about the degree of noise influence.
Evaluation of anemic syndrome (AS) was performed in 79 patients with advanced stages of Hodgkin’s lymphoma (LH) at various stages of chemotherapy (CT) according to the EACOPP-14 scheme. Against the background of the treatment, the number of erythrocytes and, accordingly, the HCT indices decreased with each subsequent cycle of chemotherapy (CTC) and reached the maximum reduction to 5, 6 th CCT. Absolute iron deficiency (IDA), which was combined with a low level of EPO and an inadequate degree of anemia, was found in a few LH patients (5 people, 6.3%). Functional iron deficiency (FDZH) was diagnosed in 9 patients (11.4%), had the same morphological signs as IDA. Namely, microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes (RET-HE). In contrast to IDA, patients with FDZh concentration of FR, GP-25 and IL-6 were high. Despite the fairly large reserves of iron, the level of rRTF testified to the “iron hunger” of the erythrocariocytes of the bone marrow, its index exceeded the upper limit of the norm, while RET-HE was low. In 34 (43%) patients, LH revealed a deficiency of endogenous erythropoietin (EPO), which was observed not only in patients with AHZ, but also in patients with IDA. Lower levels of EPO were detected in patients with leukopenia and very low erythropoietic activity of the bone marrow.