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Total number of found documents : 129
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1.

Type of document : Magazine article
Edition cipher :
Author(s) : Bilous N., Abramenko I., Chumak A., Dyagil I., Martina Z.
Title : Analysis of LPL gene expression in patients with chronic lymphocytic leukemia
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 39-45 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: The IGHV mutational status is one of the most important markers for chronic lymphocytic leukemia (CLL) prognostication. Lipoprotein lipase (LPL) gene expression was found to correlate with IGHV status and was suggested as its surrogate marker. Recent data reported that LPL expression might be influenced by pivotal signalling pathways in CLL. This study aimed to assess LPL gene expression in relation to key immunogenetic and molecular markers of CLL, including IGHV mutational status, B-cell receptor (BCR) stereotypy, TP53, NOTCH1, and SF3B1 gene mutations. Materials and Methods: Expression of LPL mRNA was measured in peripheral blood mononuclear cells of 73 CLL patients by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). IGHV, NOTCH1, TP53, and SF3B1 gene mutation analysis was performed by PCR amplification and direct sequencing. Results: 44 of 73 (60%) CLL cases were categorized as LPL-positive based on the cut-off value established by ROC (receiver operating characteristic) curve analysis. LPL expression was significantly associated with IGHV mutation status (r = 0.684; p 0.0001) and tended to correlate with presence of NOTCH1 gene mutations (p
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2.

Type of document : Magazine article
Edition cipher :
Author(s) : Alghamdi S., Tajaldeen A.
Title : Evaluation of dose calculation algorithms using different density materials for in-field and out-of-field conditions
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 46-52 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: The accuracy of the dose calculation is vital in the stereotactic ablative body radiotherapy (SABR) technique to achieve clinically effective dose distribution for better tumor control. Multiple commercial radiotherapy treatment planning systems (TPS) were implemented with different algorithms, such as Acuros XB in Eclipse and Superposition in XiO. The aim of this study is to investigate five different dose calculation algorithms, namely, pencil beam convolution (PBC), Acuros XB, AAA implemented in an Eclipse system, collapsed cone convolution (CCC) algorithm implemented in Mobius3D and superposition algorithms implemented in the XiO system, and then validate the results against measurements using an Institute of Physical Sciences in Medicine (IPSM) phantom with different density materials for in-field and out-of- field conditions. Material and Methods: The IPSM phantom was used to investigate the dose calculation algorithm performances in four different densities (water, lung, ribs, and dense bone) using different beam configurations, including small beam fields utilised in lung SABR. Five commercial algorithms implemented in two TPS (Eclipse and XiO) and one plan check (M3D) system were used for in-field and out-of-field measurement. Results: In the in-field condition, the Acuros XB algorithm had lower mean differences than the measured dose by the IC ranging from –0.46 to 0.24 for all the densities. In the out-of-field condition, the results of eclipse system: AAA, PBC and Acuros XB algorithms demonstrated underdose point’s measurements by –40% for all densities except for AAA calculations in lung density (overdosed by 40%). The measured points of the superposition algorithms were overestimated to the actual dose less than 30% in water, lung and dense bone. At the same densities, the CCC algorithms showed relatively the lowest differences in percentage compared to the superposition algorithms. Conclusion: Our results showed that the Acuros XB and superposition algorithms are closer to the actual measured dose than AAA, PBC and CCC for majority of the field conditions for water-equivalent, lung, rib and dense bone densities. The CCC algorithm resulted in a better agreement with the measurement of the out-of-field points compared with the other algorithms
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3.

Type of document : Magazine article
Edition cipher :
Author(s) : Poluben L., Bryke Ch. R., Hsu Y., Shumeiko O., Neumerzhitska L., Klimuk B., Rybchenko L., Klymenko S., Balk S. P., Fraenkel P. G.
Title : Copy number alterations and copy-neutral loss of heterozygosity in Ukrainian patients with primary myelofibrosis
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 53-56 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: To examine frequencies and spectrum of genomic alterations in Ukrainian patients diagnosed with primary myelofibrosis (PMF). Materials and Methods: We enrolled 30 Ukrainian patients diagnosed with PMF who were previously tested for usual mutations in mye­loproliferative neoplasms driver genes (JAK2, MPL and CALR). Genomic DNA samples were obtained from peripheral blood leukocytes of these patients. Copy number alterations and copy-neutral loss of heterozygosity (cnLOH) were assessed using a high-density CytoScan HD microarray platform. Statistical significance was evaluated by the Fisher exact test. Results: We identified frequent genomic alterations, but no significant difference in the rates of copy-number loss, copy-number gain, cnLOH, or multiple genomic alterations were found in the groups of PMF patients that were positive for one of the usual mutations in driver genes or negative for such mutations (33.3% and 55.6%, p = 0.4181, 19.0% and 11.1%, p = 1.0000, 61.9% and 44.4%, p = 0.4434, 33.3% and 55.6%, p = 0.4181, respectively). The most frequent alterations were cnLOH at 1p36-1p22, 9p24.3-9p13.3 and 11q12.3-11q25; copy number loss at 7q21-7q36.3 and 13q12.3-13q14.3. Copy number alterations and cnLOH commonly affected the EZH2, LAMB4, CBL, CUX1, ATM, RB1 and TP53 genes, in addition to JAK2, MPL and CALR. Conclusion: We demonstrated the spectrum of genomic alterations in the groups of the Ukrainian PMF patients with or without the usual mutations in the specific driver genes. We identified several potential genes, which may be involved in the myeloproliferative neoplasms development and their phenotype modification (EZH2, LAMB4, CBL, CUX1, ATM, RB1 and TP53)
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4.

Type of document : Magazine article
Edition cipher :
Author(s) : Stakheyeva M., Eidenzon D., Slonimskaya E., Patysheva M., Bogdashin I., Kolegova E., Grigoriev E., Choinzonov E., Cherdyntseva N.
Title : Integral characteristic of the immune system state predicts breast cancer outcome
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 32-38 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: The immune system dramatically contributes to the pathogenesis of cancer. An integral estimation of immune system state is considered to be perspective as a prognostic criterion for cancer. We hypothesize that the integral characteristic, uniting numerous parameters of immune response to tumor and presenting the state of the immune system of a cancer patient, may be of prognostic significance. The aim of this work was to verify this hypothesis. Materials and Methods: We have evaluated 17 parameters cha­racterizing key innate and adaptive arms of immune system in 146 patients with primary diagnosed local breast cancer (BC) before cancer treatment. Using the original integrative approach of NovoSpark Corporation (Canada), we have presented the state of the immune system by a single visual image for each patient. Results: We classified all BC patients in two groups: with favorable and unfavorable immune system states according to our previous data demonstrating dramatic differences of the visual images of immune system states in patients with good or poor disease outcomes. Then, we have examined the relationship between integral characteristic of the immune system state and the clinical outcome. The 3-year disease-free survival (DFS) of BC patients with favorable immune system state was more than 96.0% vs 65.4% in patients with unfavorable status (p = 0.00006). Univariate Cox proportional hazards regression analysis showed that the integral characteristic of immune system state assessed prior to cancer treatment as unfavorable, was predictive of the poorer DFS (HR = 15.70 [2.15–114.90], p = 0.0007). Conclusion: The integral characteristic of the immune system state is a significant prognostic factor in BC patients. The BC patients with favorable integral immune system state can be considered as a target group for immunotherapeutic approach
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5.

Type of document : Magazine article
Edition cipher :
Author(s) : Kolesnik D. L., Pyaskovskaya O. N., Yakshibaeva Yu. R., Solyanik G. I.
Title : Time-dependent cytotoxicity of dichloroacetate and metformin against Lewis lung carcinoma
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 14-19 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: The use of inhibitors of energy metabolism of malignant cells is a new promising trend in the treatment of cancer patients, based on one of the unique features of the malignant cell, namely the dominance of glycolysis over oxidative phosphorylation, even in the presence of oxygen, the so-called Warburg effect. Aim: To study time-dependent cytotoxicity of sodium dichloroacetate (DCA) and metformin (MTF) against metastatic tumor cells and action of these agents on tumor cell migration. Materials and Methods: In the study low metastatic LLC/R9 variant of Lewis lung carcinoma was used. The number of living cells in the cytotoxic test was evaluated using sulforhodamine B after 1, 2 and 3 days of cell incubation in vitro. The parameters of the sensitivity of tumor cells to the action of DCA and MTF in vitro were calculated using nonlinear and linear regression of experimental data. The effect of DCA and MTF on cellular motility in vitro was evaluated using a Boyden chamber by calculation of the number of cells that migrated to the bottom side of the filter within 3 days of incubation. The statistical analysis of the data was carried out with the use of descriptive methods, Student’s t-criterion, nonlinear, and linear regression analysis. Results: IC50 of DCA was found to be equal to 50.8 ± 7.6 mM at the first day of incubation with LLC/R9 cells and decreased by 1.9 (p 0.05) and 2.1 (p 0.05) times at the 2nd and 3rd days, respectively. Despite the almost identical ІC50 at the 2nd and 3rd days, an increase in the incubation period of cells with DCA for up to 3 days increased the C0 parameter, which reflects the maximum concentration of the agent that does not exhibit cytotoxic effects, by 93% (p 0.05) compared to this at the 2nd day (16.2 ± 1.4 mM vs 8.4 ± 1.0 mM, correspondently). Unlike DCA, the LLC/R9 cell population was not homogeneous by the sensitivity to the action of MTF; at least at the 3rd day, an appearance of MTF-resistant subpopulation was observed, accounting for 35% of all cells. IC50 of MTF was equal to 12.1 ± 0.6 mM, and unlike DCA, this index progressively decreased at the 2nd and 3rd days by 1.4 (p 0.05) and 9.3 times (p 0.05) respectively. Action of DCA at a concentration of 25 mM alone and in combination with MTF at the concentrations of 0.1 mM and 0.7 mM resulted in an increase in cell migration by 65% (p 0.05), 63% (p 0.05) and 78.5% (p 0.05), respectively. There was no significant effect of MTF on the tumor cell migration. Conclusions: The sensitivity of the metastatic Lewis lung carcinoma cells to the action of the modifiers of the energy metabolism increased significantly with an increase in the incubation period, apparently, primarily due to the shortage of nutrient substrates and, in particular, glucose, indicating the relevance of their combined use as well as with other agents, which promote the deficiency of glucose in the tumor microenvironment
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6.

Type of document : Magazine article
Edition cipher :
Author(s) : Lozovska Yu. V., Andrusishina I. M., Lukianova N. Yu., Burlaka A. P., Naleskina L. A., Todor I. N., Chekhun V. F.
Title : The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 20-25 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: To investigate the content of essential elements (EE): copper, zinc, magnesium, iron and calcium and the evaluation of the activity of metal-containing enzymes — ceruloplasmin (CP), myeloperoxidase (MPO) and the content of transferrin (TF) in blood plasma (BP) and tumor tissue (TT) of animals with Walker-256 carcinosarcoma treated with lactoferrin (LF). Materials and Methods: The study of the EE content and the activity of the abovementioned enzymes was carried out on rats with Walker-256 carcinosarcoma treated with LF at the doses of 1 and 10 mg/kg of body weight. The quantitative content of EE in BP and TT of animals was determined using the inductively coupled plasma atomic emission spectroscopy (ICP-AES). Determination of CP activity, content of TF and hemochromes was performed using the method of electron paramagnetic resonance (EPR), and MPO — by unified biochemical method. Results: The introduction of LF at the doses of 1 and 10 mg/kg resulted in a decrease in the ratio of Cu/Zn in BP and even more expressed decrease of Ca/Mg ratio in TT. Administration of LF, especially at a dose of 10 mg/kg, affected the increase in CP and MPO activity in BP. It has been shown that administration of LF at a dose of 10 mg/kg led to an increase in oxidative products of destruction of the hemoglobin-hemochrom system in the TT, against the background of lowering the TF content. Conclusions: The administration of LF, especially at a dose of 10 mg/kg, led to metabolic alterations associated with inhibition of the tumor process. The detected modulating effect of LF on the content of the EE and the activity of the CP and MPO may be a basis for correction of the elemental balance in carcinogenesis
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7.

Type of document : Magazine article
Edition cipher :
Author(s) : Burlaka A. A., Vovk A. V., Burlaka A. P., Kolesnik O. O.
Title : DNA oxidation in patients with metastastic colorectal cancer: clinical significance of 8-hydroxy-deoxyguanosine as an independent prognostic factor
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 26-31 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: Prognosis of metastatic colorectal cancer (mCRC) patients nowadays is an important subject in the field of oncology. R0-resection of colon with primary tumor and liver metastasis remains the only treatment which significantly improves survival rate. However, recent experimental data show that surgical trauma can indirectly stimulate tumor growth due to mitochondrial dysfunction and unregulated superoxide radical (O2-) generation. Aim: To study the clinical significance of 8-oxo-2'-deoxyguanosine (8-oxodGu) marker, to assess the oncological effects of warm ischemia of liver parenchyma on disease prognosis in patients with mCRC. Material and Methods: 69 urine 24-hour volume tests of patients with mCRC and 17 healthy individuals were studied. Urine 8-oxodGu level was measured using spectrophotometric method with pre-solid phase DNA extraction. The energy system and hepatocyte detoxification system state, levels of O2- in tumor tissue were determined using the method of electron paramagnetic resonance (EPR) and SpinTraps technology at room temperature. Experiments were carried out on a computerized EPR spectrometer RE-1307. EPR spectra were recorded at temperature of liquid nitrogen (–196 °C) in paramagnetically pure quartz dewar on a computerized spectrometer PE-1307 with resonator H011. Error of the method of spectrum integration and spread of spectrum reproduction of one sample was not more than 3%. Results: The average level of marker in healthy individuals was 0.244 ± 0.063 nM/kg ∙ day, whereas before the resection and on day 3 after the R0-resection of liver in mCRC patients was 3.42 ± 0.18 nM/kg ∙ day and 2.12 ± 0.08 nM/kg ∙ day (p 0.05), respectively. On day 3 after the liver resection due to its metastatic lesions with a total duration of warm ischemia period 30 min and 30 min have had marker at level 2.108 ± 0.13 nM/kg ∙ day and 2.9883 ± 0.159 nM/kg ∙ day (p 0.0001), respectively. The volume of metastatic tissue significantly and directly correlated with the level of urine 8-oxodGu (R2 30 min) during the surgery significantly increased urine level of 8-oxodGu (R2 = 0.54, 95% CI 0.001–0.004, p 0.001). Conclusions: Warm liver ischemia ( 30 min), long-term surgical intervention (≥ 300 min) and metastatic tissue volume (≥ 12 cm3) in liver parenchyma in mCRC patients significantly increase urine 8-oxodGu levels. R0-resection of liver metastases in mCRC patients decreases urine 8-oxodGu levels already on day 3 after the surgery. 8-oxodGu is a new factor of oncological prognosis in patients with mCRC
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8.

Type of document : Magazine article
Edition cipher :
Author(s) : Bakai O. A., Golovko T. S., Ganich A. V., Gavriluk O. N., Ashykhmin A. V.
Title : Radiation research to determine local tumor invasion in patients with cervical cancer
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 57-60 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: The main task of radiation study of verified cervical cancer (CC) is tumor spread assessment because of its profound effect on the treatment tactics choice and prognosis. The Aim of the study was radiation study optimizing for tumor local spread assessment in patients with CC via comparing the usefulness of different magnetic resonance imaging (MRI) based approaches. Materials and Methods: 62 patients with CC were examined by MRI on tomograph 1.5 Т using contrast enhancement and diffusion-weighted imaging (DWI). Pre-operation data on radiation diagnostics of tumor spread were compared with surgical and pathologic data. Results: The diagnostic efficiency of different methods of radiation testing for assessment of local tumor spread in patients with CC was determined. The use of contrast enhancement didn’t increase an informative value of МRI in assessment of local tumor spread. False overestimation of tumor spread was caused by intense accumulation of contrast substance around the tumor due to inflammation. Use of DWI allowed to reduce the number of false positive results, and significantly increased the efficiency of MRI (p 0.05): the positive predictive value, sensitivity, specificity and accuracy were 83.3; 90.9; 96.0 and 95.1%, respectively. Conclusions: The use of DWI increases informativeness of МRI in assessment of local tumor spread
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9.

Type of document : Magazine article
Edition cipher :
Author(s) : De Giorgi V., Scarfì F., Silvestri F., Maida P., Gori A., Trane L., Massi D.
Title : Cutaneous leiomyosarcoma: a clinical, dermoscopic, pathologic case study
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 80-81 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: Cutaneous leiomyosarcoma is a rare malignant mesenchymal tumor of smooth muscle origin of unknown etiology. Leiomyosarcomas located on the skin include superficial leiomyosarcomas and metastatic leiomyosarcomas. Superficial leiomyosarcomas represent 7–10% of all cases of leiomyosarcoma and are subdivided into cutaneous and subcutaneous lesions based on skin location. We report a case of an 81-year-old woman who presented a slow growing tender single nodule on the left thigh and describe its clinical and dermoscopic features
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10.

Type of document : Magazine article
Edition cipher :
Author(s) : Langabeer S. E., Haslam K., Crampe M., MacDonagh B., McHugh J.
Title : Suboptimal molecular response to tyrosine kinase inhibition associated with acquisition of a T240A ABL1 kinase domain mutation in a patient with chronic myeloid leukemia
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 82-83 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: Over the last twenty years, chronic myeloid leukemia (CML) has come to be considered a paradigm for rationally selected, targeted inhibition of the disease-specific, BCR-ABL1 tyrosine kinase activity. However, a minor but significant numbers of patients either fail, or have suboptimal responses to first line tyrosine kinase inhibitor (TKI) therapy. The causes of a suboptimal response are many, with the acquisition of ABL1 kinase domain mutations (KDMs) contributing to resistance being widely studied. These ABL1 KDMs usually become apparent within the first two years of starting TKI therapy and their discovery has led to the development of second and third generation TKIs [1]. ABL1 KDMs have been detected throughout the kinase domain with ten common mutations accounting for the majority of those observed [2]. However, rare and novel mutations continue to be detected in TKI-resistant patients with reporting of such cases necessary for future understanding of real-world CML patient managementA 44 year-old man presented with fatigue, weight loss, night sweats, abdominal discomfort, and a hemoglobin of 9.9 g/dl, white cell count of 353.9•109/l and platelet count of 130•109/l. The patient had a marked splenomegaly detected 17 cm below the costal margin. Bone marrow aspirate showed hypercellularity, myeloid metaplasia, only 1% basophils and no myeloblasts with cytogenetics detecting the t(9;22) translocation in all metaphases analysed. Quantitative reverse-transcription polymerase chain reaction detected e13a2 BCR-ABL1 transcripts at a high level, all consistent with a diagnosis of high-risk (Sokal score 1.5; EUTOS score 88), chronic phase CML. The patient commenced nilotinib 300 mg twice daily with BCR-ABL1 transcript levels decreasing very slowly (Figure). Within the first year of treatment he experienced intermittent eye irritation, conjunctival hyperemia which required occasional steroid eye drops and ocular lubricant, and a persistent sensation of asthenia with regular myalgias. His peripheral blood BCR-ABL1 transcript level (Internationally Standardised) at twelve months was a suboptimal 4.87% prompting switch to dasa­tinib 100 mg once daily increased to 140 mg once daily. At twenty months post-diagnosis, the BCR-ABL1 transcript level was 2.12% triggering analysis for an ABL1 KDM as previously described [4] and of which no mutation was detected (Figure). Despite a continued slow decline in BCR-ABL1 transcripts, a major molecular response was never achieved with re-analysis for an ABL1 KDM at 47 months detecting an ABL1 T240A mutation (c.718AG, p.Thr240Ala; reference sequence NM_005157.5). The patient is currently well with persistent thrombocytopenia secondary to dasatinib and occasional myalgias. He continues attending for regular close molecular monitoring with a most recent BCR-ABL1 level of 0.15% five years post diagnosis
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