Cytokines and chemokines play dual – pro- and antioncogenic – roles in tumor progression. Targeted medications of monoclonal antibodies, anti-VEGF (bevacizumab) and anti-EGFR (cetuximab, ...panitumumab), are widely used in treatment of metastatic colorectal cancer (mCRC) and are prescribed in dependence upon presence or absence of mutations in the RAS gene. The aim of the study was to assess mCRC heterogeneity in the dependence upon presence or absence of mutation in RAS gene according to serum cytokine composition and its dynamics in the response to antitumor therapy using targeted medications of monoclonal antibodies. Levels of 20 cytokines were estimated by Multiplex analysis in serum of 50 patients with mCRC (25 KRAS + and 25 KRAS - , who received anti-VEGF therapy, bevacizumab and anti EGFR therapy, cetuximab/ panitumumab respectively) before and after 4 courses of treatment. The results were analyzed separately in patients with complete, partial response and progression of the disease. The results showed that before the treatment in KRAS + patients the levels of GM-CSF, IL-2, IL-5, IL-6, IL-7, IL-10, and IL-13 exceeded the ones in KRAS- patients; on the contrary, they had lower amounts of IL-8, IP-10, MIG, and MIP-1α. In patients who received anti-EGFR therapy and developed complete response, the increase of IL-15 and MIG along with a 2 to 3-fold decrease in GM-CSF, IL-2, IL-4, IL-6, IL-8, IL-17А, and МСР-1 was noted. Progression of the disease was observed in patients with initially low levels of the vast majority of the studied cytokines with dramatically elevation after non-effective anti-EGFR treatment. In patients having received anti-VEGF therapy, progression was followed by decrease in all of the studied cytokine and chemokine levels, while complete response resulted in decreases in IL-6, IL-5 and IL-10 (the last ones up to 0) and the increase of MIG. Thus, serum levels of cytokines in patients with mCRC were shown to be different in dependence of KRAS mutation; different response to targeted monoclonal antibodies may be reflected by the dynamics of serum cytokines` composition. Prevailing of many prooncogenic and proangiogenic cytokines in KRAS + mCRC patients may be considered in terms of their unfavorable prognosis.
Specific prevention is one of the most effective methods for the control of infectious diseases causing considerable economic damage to commercial pig farms, among which is porcine pleuropneumonia. ...In order to improve the effectiveness of preventive vaccination, various immunomodulators that differ in their origin and mechanism of action are used. The paper presents the results of the study of the effect of such products as biferon-S and prostimul containing species-specific recombinant interferons on the immune status of piglets during specific prevention of porcine pleuropneumonia. Tests were carried out in clinically healthy 30–35-day-old piglets immunized with Ingelvac
®
APPX vaccine (Boehringer Ingelheim Vetmedica GmbH, Germany). It was found that the use of biferon-S and prostimul together with the vaccine administration is accompanied by immune status improvement in the animals, which is manifested as an increase, in comparison with vaccinated animals that received no interferon-containing products (base case), in serum levels of γ-globulins – by 34.6 and 53.7% (in case of prostimul and β-globulins – by 10.1%), total immunoglobulins – by 32.8 and 37.8%, large circulating immune complexes – by 37.5 and 52.6%, a less significant increase in the levels of small complexes and, as a result, pathogenicity coefficient reduction by 5.4 and 12.4%, respectively. Tests for post-vaccination immunity levels in piglets showed a 3.8-fold increase in the levels of specific antibodies against the antigen of porcine pleuropneumonia agent, and in case of the vaccine administration in combination with biferon-S and prostimul – a 4.0-fold and 4.9-fold increase, respectively. The use of prostimul was accompanied by a more considerable improvement of immune status in the piglets, and this is attributable to the fact that vitamins А, Е and С, which have antioxidant properties and improve the effectiveness of interferons, natural resistance and specific immunity, are included in its composition in addition to recombinant type 1 cytokine.
Purpose of the study.
This work is devoted to the study of blood plasma miRNA patterns in blood plasma using high-throughput sequencing of the Omnibus Gene Expression base and the search for ...candidate miRNA molecules for the development of a minimally invasive diagnostic panel.
Materials and methods.
Basing on the open dataset of Omnibus Expression of the NCBI GSE150956 Gene, groups of samples with glioblastoma and conventionally healthy donors were formed. For each sample, information on the levels of miRNA expression was extracted. Determination of significant miRNAs using machine learning algorithms of the R 4.0.4 project. For significant miRNAs, target genes have been performed, an analysis of the improvement of functional characteristics and interactome analysis of target genes of miRNA were performed.
Results
. The study analyzed the data of 131 samples, where 35 samples with glioblastoma and 96 samples of the conditionally healthy group. Differential expression data were obtained for 945 miRNA. Two panels were obtained using machine learning methods, common miRNA – hsa-miR 3180, hsa-miR 3180-3p, hsa-miR 6782-5p, hsa-miR 182-5p, hsa-miR 133b and hsa-miR 670-3p. For significant miRNAs, information was obtained on experimentally confirmed target genes, a gene ontology demonstrating their participation in enzyme binding, participation in the regulation of primary cellular metabolic processes, and the development of glioblastomas and cancer in general.
Conclusion
. As a result of layer-by-layer filtering and application of machine learning algorithms, significant miRNAs were identified that are candidates for a diagnostic panel of a minimally invasive method of high-grade glial tumors.
The development of a new area of antitumor drug therapy, immunotherapy using immune checkpoint inhibitors targeting PD-1/PD-L1, has significantly changed approaches to the treatment of advanced ...non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated the clinical benefit as well as the long-term effect of these drugs. Currently, the problem of treatment of patients after disease progression against the background of the use of checkpoint inhibitors is relevant. Equally relevant is the issue of choosing the correct and most effective treatment tactics for NSCLC patients with oligoprogression, as well as with abscopal effect. This paper describes a clinical case of a patient with lung adenocarcinoma without driver mutations with PD-L1-positive status, who was treated with nivolumab after second-line chemotherapy for disease progression, and after oligoprogression of the disease into the brain was given stereotactic radiotherapy of metastatic lesion and continued therapy with nivolumab. Partial regression of metastases was achieved with a prolonged effect on the background of continued treatment with nivolumab for 24 months. Tolerability of therapy was satisfactory: no adverse events were observed. The patient retained the result for 1.5 years.
The purpose of this study was to research the effectiveness of molecular genetic tests based on the determination of the rs4673 CYBA polymorphism (c.242C>T) and the level of paraoxonase 1 (PON1) in ...the blood plasma of patients with breast cancer (BC) for predicting and diagnosing anthracycline-mediated cardiotoxicity (AMC). The genotyping of rs4673 CYBA (c.242C>T) and the study of the PON1 level in the blood plasma of 280 patients of the Caucasian type with a histologically verified diagnosis of breast cancer, who received complex treatment on the basis of the National Medical Research Center of Oncology, were carried out. Based on the results of observation for at least 8 months, two groups were identified: group 1 (257 people) without diagnosed cardiovascular changes; group 2 (23 people) - patients with subacute and early chronic AMC. It was found that carriers of the rs4673 polymorphism increase the likelihood of developing AMC by 6.8 times (p = 0.001). In the blood plasma of both groups of patients, an increase in the level of PON1 was described after the fourth course compared to the initial level (group 1 - p = 0.036, group 2 - p = 0.048). The level of the studied enzyme was higher in the blood plasma of patients with diagnosed AMC compared with patients without cardiovascular complications (before chemotherapy - p = 0.001, after the fourth course - p = 0.023). The test based on the measurement of the concentration of PON1 in the blood plasma of patients after the fourth course of chemotherapy was distinguished by high quality metrics: sensitivity - 100%, specificity - 70.8%, area under the ROC-curve (AUC) - 0.825 with a threshold level of PON1 equal to 2, 9 ng/μL. The presence of the T/T genotype caused a high level of PON1 in the blood plasma after the fourth course of chemotherapy (p = 0.012). The results of our work are of undoubted practical importance, since they allow us to obtain data on the prognosis and diagnosis of a patient in a short time, which can later be verified using clinical and instrumental methods.
The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of
NTRK
gene translocations in patients ...with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by
NTRK
gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by
NTRK
gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of
NTRK
gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by
NTRK
gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months.
The aim.
To analyze the blood levels of endothelin-1 (ET -1) and high molecular weight kininogen (HMWK) in patients with breast cancer (BC) previously infected with the new coronavirus.
Material and ...methods.
The study group included 20 patients with stage II -IV BC (invasive carcinoma). All patients were receiving chemotherapy at the time of their SA RS-CoV-2 infection. The comparison group included 19 women without breast cancer, who were matched for age. All women of both groups had an RT-PC R confirmed SA RS-Cov-2 infection. Blood levels of ET -1 and HMWK were measured by ELISA 3–10 weeks after the positive antigen test results. The control group included 10 women of the same age without cancer and without CO VID -19 symptoms and anti-SA RS-CoV-2 antibodies.
Results.
The ET -1 levels in the comparison group were within the reference range, while HMWK levels were significantly higher than those in breast cancer patients. In BC patients with lung metastases, the ET -1 levels were higher than those in the comparison group patients, while in others (no history of lung metastases, with mild infection course or pneumonia), the ET -1 levels were similar to those in the comparison and control groups. The HMWK levels in the study and comparison groups were significantly higher than those in controls. Among BC patients, there were women who had significantly higher ET -1 and HMWK levels compared to the reference levels, and the majority of these patients had lung metastases and previous CO VID -19 pneumonia.
Conclusion.
The measurement of HMWK blood levels demonstrated that the plasma contact activation system and the kallikrein-kinin system were active for a long period after the infection both in BC patients and in women without cancer. A high level of ET -1, the endothelial dysfunction marker, persisted for a long time in some BC patients. Our results were consistent with results of other studies supporting the hypothesis that SA RS-CoV-2 virus infection is a systemic vascular disease with long-term consequences, and its mechanisms require further study.
Introduction
. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.
The purpose of study
. Clinical evaluation of the efficacy and safety of Eralfon® ...(epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.
Materials and methods
. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.
Results
. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.
Conclusion
. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.
Purpose of the study. An analysis of changes in the expression of the VEGF neoangiogenic factor in the tumor tissue of patients with squamous cell carcinoma of the oral mucosa receiving targeted ...therapy with cetuximab and chemotherapy.Patients and methods. We performed an immunohistochemical study of tumor samples obtained from 60 patients with squamous cell carcinoma of the oral mucosa T3-4N0-1M0. The main group comprised 30 patients who received therapy with cisplatin and fluoruracil plus cetuximab. The control group included 30 patients receiving standard chemotherapy without targeted therapy. Each group was divided into two subgroups with different treatment efficacy: patients sensitive to treatment (n = 17 in the group with cetuximab and n = 12 in the group without cetuximab) and resistant to treatment (n = 13 in the group with targeted therapy and n = 18 in the group with standard chemotherapy).Results. Quantification of the VEGF expression demonstrated minimal numbers of vessels stained positively for this marker in the field of view in patients of the main group sensitive to chemotherapy and cetuximab. The value was 5.3 times lower than initial values, and 4.3 times lower than in the subgroup of patients resistant to the treatment (the data were statistically significant, р = 0.0132 and р = 0.0455, respectively). In the control group, patients who were sensitive to the treatment showed 1.4 times lower values than initially (р = 0.921), and patients who were resistant to the treatment had 1.1 times lower values than initial values (р = 0.936). The data were not statistically significant.Conclusions. The study showed that the number of microvessels in patients resistant to chemotherapy and cetuximab was 4.3 times higher than in patients with effective targeted therapy (р = 0.0455). The differences in the control group were not statistically significant.
Introduction:
Squamous cell carcinoma of the oral cavity is one of the most common head and neck cancers with an aggressive course and high mortality rates.
The aim
of the study was to determine the ...EGFR expression levels in tumor tissues in patients with squamous cell carcinoma of the tongue and oral mucosa depending on the efficacy of the therapy.
Material and methods:
The study included 60 patients with squamous cell carcinoma of the tongue and oral mucosa T3-4N0-1M0. The main group included 30 patients receiving chemotherapy (cisplatin/fluorouracil) in combination with targeted therapy with cetuximab. The control group included 30 patients receiving chemotherapy without cetuximab. Both groups were divided into two subgroups: sensitive and resistant.
Results:
In treatment-resistant patients of the main group with cetuximab, the average EGFR expression was twice lower than the initial levels (p = 0.0080) and 1.7 times higher than in treatment-resistant patients of the control group (p = 0.0157). In treatment-sensitive patients, the average EGFR expression was 19.8 times lower (p = 0.0020) than initial values and 14.9 times higher (p = 0.0067) than in treatment-sensitive controls.
Conclusions:
A natural decrease in the EGFR expression in tumor tissues due to the targeted therapy was revealed. However, some patients were resistant to cetuximab, which dictates the need to search for predictors of targeted therapy efficacy in patients with locally advanced squamous cell carcinoma of the tongue and oral mucosa.
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