bluuebunny/crossref_metadata_2025 huggingface dataset:
EPR SPECTROSCOPY STUDIES OF CHANGES IN ERYTHROCYTE MEMBRANES IN PATIENTS WITH LARYNGEAL CANCER
Authors: Burlaka Y B , Sukhoveev O V , Grin N V , Khilchevskyi O M , Verevka S V
Published: January 2019

Aim: To evaluate microviscosity and sorption capacity of erythrocyte membranes (SCEM) from patients with laryngeal cancer (LC). Materials and Methods: Samples from 35 patients with LC of stages II and III and 20 healthy volunteers were investigated by electron paramagnetic resonance with Bis(1-oxyl-2,2,6,6-tetramethylpiperidinyl-4)-ester of 5,7-dimethyladamantane-1,3-dicarbonic acid (AdTEMPO) probe. SCEM was evaluated by amount of unabsorbed methylene blue. Results: Microviscosity of erythrocyte membranes was determined by the effective rotational diffusion correlation times (τeff) and a decrease in radical spectrum signal intensity per hour. The most apparent decrease in mobility of the AdTEMPO in erythrocytes was observed prior to washing of erythrocytes with 0.9% NaCl for 5 min after probe insertion. The deceleration after 60 min was observed only in stage II LC. τeff was at control values after washing of erythrocytes of stage II LC 5 min after probe insertion and was significantly reduced in stage III LC in comparison to control. Radical spectrum signal intensity per hour in samples of stage II and III patients prior to and after washing of erythrocytes was on average 1.5-fold higher than that of control. SCEM in samples of stage II and III LC was found in 40 and 33% cases, respectively and was on average significantly reduced in comparison to control. Conclusions: The initial interaction of AdTEMPO with erythrocyte membranes of stage II and III LC patients is accompanied by an increase in τeff, indicating deceleration of probe rotation. τeff of the probe in membranes remains unchanged in 60 min, indicating changes in the structural organization of lipid bilayer and its associated proteins in particular. The similarity of SCEM for both studied groups reflects the pathological changes in function of erythrocyte membranes.
ABERRANT PROMOTER HYPERMETHYLATION OF SELECTED APOPTOTIC GENES IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA AMONG NORTH INDIAN POPULATION
Authors: Nikbakht M , Jha A K , Malekzadeh K , Askari M , Mohammadi S , Marwaha R K , Kaul D , Kaur J
Published: January 2019

Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. Aim: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). Materials and Methods: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. Results: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. Conclusions: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.
SIGNIFICANCE OF IODINE SYMPORTER FOR PROGNOSIS OF THE DISEASE COURSE AND EFFICACY OF NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER OF LUMINAL AND BASAL SUBTYPES
Authors: Chekhun V F , Andriiv A V , Lukianova N Yu
Published: January 2019

The aim of the research was to study the relation between expression of Na+/I- symporter (NIS) in breast cancer (BC) of different molecular subtypes and sensitivity of BC cells to neoadjuvant chemotherapy (NACT) and to assess whether NIS expression may be used as a predictive marker of treatment efficacy. Materials and Methods: The study included 148 women with BC of stage II–III who were treated at the Precarpathian Clinical Oncology Center during 2012–2017. All patients were treated with NACT that included 2–6 cycles of chemotherapy by FAC, AC scheme with 21 day intervals. NACT efficacy was evaluated every 2 cycles by mammography according to RECIST criteria. Morphological and immunohistochemical study of NIS expression was performed by the standard methods on paraffin sections of surgically resected tumors. Results: The heterogeneity of different molecular BC subtypes regarding response to the NACT has been found. Her2/neu-positive and basal BC subtypes were the least susceptible to the NACT (p < 0.05). It was shown that NIS expression is related to the sensitivity of luminal B and basal BC subtypes to the NACT. The highest expression of NIS and impairment of its functional activity was registered in the group of patients with tumors resistant to NACT (stabilization of the disease or its progression) of luminal B (220 ± 8.6 points) and basal subtypes (290 ± 11.3 points) (p < 0.05). It was revealed that the disease-free survival of patients with BC of luminal B and basal subtypes was higher in the absence of NIS expression in tumor cells (p < 0.05). Conclusions: The results indicate that NIS can be used as an objective criterion for predicting the sensitivity of luminal B and basal BC subtypes to NACT, which will provide improved treatment outcomes in this group of patients.
TRICHILEMMAL CYSTIS IN METASTATIC MELANOMA: A CASE REPORT
Authors: Savarese I , Grazzini M , Gori A , D’Errico A , Doni L , Scarfì F , Covarelli P , Di Costanzo F , De Giorgi V
Published: January 2019

The malignant melanoma is a neoplasm associated with a wide variety of cutaneous paraneoplastic syndromes, as dermatomyositis, systemic sclerosis, paraneoplastic pemphigus. We describe a case of four multiple trichilemmal cystis arising on frontal region in the same patient with brain metastasis and unknown primary melanoma and discuss their relationship.
EXPERIMENTAL STUDY OF LIPOSOMAL DOCETAXEL ANALYSIS OF DOCETAXEL INCORPORATION AND STABILITY
Authors: Krasnopolsky Y M , Dudnichenko A S
Published: January 2019

Aim: The article presents the results of developing the composition and technology of obtaining the liposomal form of docetaxel. The effect of the phospholipid composition of the membrane, ionic strength, pH, temperature, cryoprotectant type, and other factors on the stability of liposomes and the docetaxel incorporation has been considered. Results: Reduction of toxicity of the liposomal form of docetaxel (LD50 — 137 ± 7.7 mg/kg) was found in comparison with its free form (LD50 — 101 ± 6.3 mg/kg). Preservation of nanosize particle after lyophilization has been shown. Conclusions: As a result of the studies, the optimal composition and technological scheme for obtaining liposomes containing docetaxel have been developed allowing large-scale production of docetaxel in liposomal form.
LECTIN BINDING PATTERNS IN NORMAL, DYSPLASTIC AND HELICOBACTER PYLORI INFECTED GASTRIC MUCOSA
Authors: Vernygorodskyi S , Shkolnikov V , Suhan D
Published: January 2019

Aim: To analyze the glycoprotein binding sites of the gastric mucosa and its secreted mucus using lectin histochemistry in patients with chronic non-atrophic gastritis (CNAG) associated or not-associated with Helicobacter pylori infection with or without dysplasia. Materials and Methods: In order to identify the areas with glycoconjugates expression in gastric mucosa, 6 lectins (Canavalia ensiformis agglutinin — Con A, Sambucus nigra agglutinin — SNA, wheat germ agglutinin — WGA, soybean agglutinin — SBA, Helix pomatia agglutinin — HPA, peanut agglutinin — PNA) were used. Carbohydrate determinants were visualized according to the lectin-peroxidase-diaminobenzidine staining protocol. Biopsy material was obtained and processed by conventional histological methods. The samples from 84 patients (54 with CNAG) with low (n = 34) and high grade (n = 20) dysplasia, 38 patients were H. pylori-infected and 26 patients — H. pylori-noninfected) were used. The comparison group included 30 persons with CNAG without dysplasia (16 patients H. pylori-infected and 14 — noninfected). Results: In comparison to normal gastric mucosa, a low affinity of Con A was shown in 80% of patients with non-infected CNAG and 90% of H. pylori associated CNAG. In 70% of H. pylori-infected patients with CNAG and low grade dysplasia there was an increase of SNA expression compared with noninfected patients (p < 0.05). Regarding SBA labeling no differences were detected in the studied groups (p < 0.05). In H. pylori infected patients with CNAG and low grade dysplasia, WGA, HPA and PNA showed a strong reactivity with the gastric mucosa cells in 80; 75%, and 60% of patients, respectively. Conclusion: We suggest that a set of lectins in reaction with gastric epithelial and glandular cells can be used as a tool to obtain information about the dysplastic changes of the gastric mucosa and may offer new insight into gastric carcinogenesis and precancerous lesions treatment.
GENERIC IMATINIB IN THE TREATMENT OF CHRONIC MYELOID LEUKEMIA: TWO YEARS’ EXPERIENCE IN LATVIA
Authors: Lejniece S , Udre I , Rivkina A
Published: January 2019

Background: Imatinib is tyrosine kinase inhibitor (TKI) and as a targeted anti-cancer agent has significantly changed chronic myeloid leukemia (CML) prognosis and patient survival. Currently TKI is the main therapy in CML Philadelphia chromosome-positive (Ph-positive) cases. When generics of imatinib appeared in the pharmaceuticals market, reimbursement policies in many countries switched to using generics or encouraged use of generic imatinib to lower the expenses. Cost savings were substantial; however, for doctors and CML patients the efficacy, safety and quality of generic imatinib were an issue of concern. Objective: Since the global number of CML patients, who in the future will have to switch from original imatinib to generic imatinib, is high, the aim of study was to monitor, whether during 24 months of generic imatinib usage patients maintain the achieved major molecular response (MMR) or whether the treatment results are inferior. Methods: We conducted a retrospective study, which included CML patients, who were above 18 years of age and who until May 2013 had used at least for 2 years (24 months) the original imatinib, and following that used at least for 24 months one of the generic imatinib medicines. In 2013, before switching to generic imatinib, all patients had reached MMR in accordance with European LeukemiaNet (ELN) Guidelines. Every three months blood count, BCR-ABL fusion gene (BCR-ABL), biochemical analysis and side effect were monitored. Results: Our study proved that CML patients, who had achieved MMR by original imatinib therapy, retained MMR during 24 months of generic imatinib therapy. Nobody was switched to second line generation TKI. During observation period neither haematological, nor non-hematological toxicity was found. Conclusion: Our study proved that CML patients, who had achieved MMR by original imatinib therapy, retained MMR during 24 months of generic imatinib therapy. This demonstrates that generic imatinib is not inferior to original imatinib. As to expenses, the annual costs of generic imatinib are lower by 96%, which is a significant benefit to health-care financing.
ASSESSMENT OF THE EFFECT OF WAVE DEVICE APPLICATION ON MORPHOLOGICAL CHANGES IN ORGANS AND CELLS OF IRRADIATED ANIMALS
Authors: Bebeshko V , Homolyako I , Grynchyshyn V
Published: January 2019

Aim: To study the effect of the Device for wave influence on biological objects on the prevention of the development of acute radiation sickness and chronic radiation syndrome in vivo. Materials and Methods: The studies were performed on white rats irradiated at a dose of 8 Gy. The experimental group of irradiated rats was treated with a wave Device (Patent of Ukraine No. 53568) once, for 2.5 min, 1.5 h after irradiation. Their organs were processed by standard histologic methods. Results: In the demagnetized rats, dystrophic changes in cells and tissues of liver, lungs, kidneys, brain, bone marrow and spleen were insignificant in 60 days compared to the control non-demagnetized group of animals. Conclusion: The Device reduced the magnetic charge of magneto-containing elements and their compounds in the organism of the irradiated animals, and decreased the formation of reactive oxygen species, which play a key role in the development of radiation-induced diseases.
THE TGF-BETA — SMAD PATHWAY IS INACTIVATED IN CRONIC LYMPHOCYTIC LEUKEMIA CELLS
Authors: Matveeva A , Kovalevska L , Kholodnyuk I , Ivanivskaya T , Kashuba E
Published: January 2019

Aim: To study the status of the tumor growth factor beta (TGFB) pathway in chronic lymphocytic leukemia (CLL) cells and to uncover molecular details underlying CLL cell genesis. Objects and Methods: The study was conducted on peripheral blood samples of patients with CLL using the following methods: RNA isolation, analysis of expression of transcription factors using RT2 profiler assay, bioinformatics analysis of publicly available data bases on expression. Results: We have shown that the TGFB — SMAD canonical pathway is not active in CLL cells. SMAD-responsive genes, such as BCL2L1 (BCL-XL), CCND2 (Cyclin D2), and MYC, are down-regulated in CLL cells compared with peripheral blood B cells of healthy donors. Conclusions: The TGFB-mediated signaling is not active in CLL cells due to low (or absent) expression of SMAD1, -4, -5, -9, and ATF-3. Expression and phosphorylation status of SMAD2 and -3 should be further elucidated in the future studies.
ADSORPTION-RHEOLOGICAL PROPERTIES OF BLOOD SERUM IN LUNG CANCER PATIENTS
Authors: Dumanskiy Y V , Stoliarova O Yu , Syniachenko O V , Giulmamedova M F , Potapov Y A
Published: January 2019

The aim and objectives of the study were to investigate the state of adsorption-rheological properties of blood (ARPB) in patients with different clinical course of lung cancer (LC), the detection of violations of surface-active, viscoelastic and relaxation properties of blood serum, their association with tumor markers, the evaluation of the prognostic value of initial indexes in the development of complications from radiochemotherapy. Patients and Methods: The study included 115 patients with LC at the age from 24 to 80 years (average age 58 years), among whom there were 78% men and 22% women. The parameters of surface (interfacial) viscosity, elasticity, viscoelasticity module, tension and relaxation of blood serum were studied by the oscillating drop method using a computer tensiometer “PAT2-Sinterface”, and its volumetric viscosity was investigated using a Low-Shear-30 rotational viscometer. ARPB parameters were also studied in a control group composed from 50 healthy donors. Results: Increased levels of volumetrical viscosity, surface tension, surface elasticity and the relaxation time of the blood are typical for patients with LC and depended on the localization of the tumor, its histological variant, differentiation grade, severity of the course of the disease, the number of metastases in the lymph nodes, distant organs and skeleton, involvement of the pleura and ribs, the development of compression pulmonary syndrome, metastasis into the spine, adrenals, brain, and pancreas. The surface-active, viscoelastic and relaxation properties of the blood correlated with the levels of tumor markers (TGFβ1, VEGF, C-reactive protein, α2-macroglobulin). Conclusions: Integral changes of ARPB observed in every fifth patient with LC are involved in the pathogenesis of the disease, have predictive value in relation to the clinical course of disease (volumetric viscosity) and the development of complications from radiochemotherapy (surface viscosity).
SIGNATURES OF ANTI-THOMSEN — FRIEDENREICH ANTIGEN ANTIBODY DIVERSITY IN COLON CANCER PATIENTS
Authors: Krutenkov O , Bubina M , Klaamas K
Published: January 2019

Aim: To determine whether the structural and functional diversities of naturally occurring antibodies to the Thomsen — Friedenreich (TF) antigen may be of diagnostic and prognostic value in colon cancer. Materials and Methods: Serum samples were taken from patients with colon cancer (n = 94) and healthy controls (n = 64). The level of TF-specific antibody isotypes and their sialylation were determined using ELISA and lectin-ELISA with synthetic TF-polyacrylamide conjugate as an antigen and a sialic acid-specific Sambucus nigra agglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope. The accuracy of diagnostics was evaluated using the receiver operator characteristic curve analysis and the survival analysis employing the Kaplan — Meier method. Results: Compared to healthy controls, patients with colon cancer exhibited a lower level of anti-TF IgG antibodies, significantly lower ratios of TF-specific IgG/IgM and IgG/IgA, an increased SNA reactivity of anti-TF antibodies, mostly on account of IgG, and a lower avidity of TF-specific antibodies, especially their SNA-reactive subset. An increased SNA reactivity of anti-TF IgG was observed already at the early stages of cancer (p = 0.0004). The decrease of the ratio of IgG/IgM and IgG/IgA showed a good accuracy of diagnostics with about 60% sensitivity at 90% specificity. A similar potential was found for the SNA binding/IgG level index. The high level of TF-specific IgA antibodies was associated with a lower survival rate (hazard ratio = 0.34). Conclusion: This is the first report ever on the colon cancer-related signatures of anti-TF antibody diversity which show diagnostic potential, including in early cancer, and prognostic value. The hypersialylation of TF-specific antibodies appeared to be a common phenomenon in cancer. The signatures may be used as non-invasive antibody-based markers for colon cancer.
A LONG SURVIVAL OF A PATIENT WITH BRAIN METASTASIS OF UNKNOWN SITE OF THE PRIMARY TUMOR
Authors: Ben Kridis W , Sghaier S , Toumi N , Boudawara Z , Khanfir A , Daoud J , Frikha M
Published: January 2019

Eighty percent of brain metastases (BM) are diagnosed in patients with known primary site of cancer. BM of unknown primary represents a difficult diagnosis. In up to 15% of patients with BM, the site of the primary tumor will not be detected despite investigations. The prognosis of this entity is very poor. We report here a case of a long survival of a patient with brain metastasis of unknown primary. The conclusion that can be drawn is that within BM of unknown primary exist patients with a very good prognosis that must be collected and published in order to base recommendations.
INCREASED HOMOCYSTEINE PLASMA LEVELS IN BREAST CANCER PATIENTS OF A MEXICAN POPULATION
Authors: Varela Almanza K M , Puebla-Perez A M , Delgado-Saucedo J I , Rodriguez-Arevalo F , Zuniga-Gonzalez G M , Figuera L E , Moran-Mendoza A , Gallegos-Arreola M P
Published: January 2019

Aim: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. Materials and Methods: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. Results: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. Conclusions: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population.
THE STATE OF BONE METABOLISM IN LUNG CANCER PATIENTS
Authors: Dumanskiy Y V , Syniachenko O V , Stepko Ph A , Taktashov G S , Chernyshova O Y , Stoliarova O Y
Published: January 2019

In recent years, we have discussed the correlation of malignant tumor process with the development of osteoporosis, which can be exacerbated by ongoing chemotherapy and radiation therapy. The aim of the work was to assess the status of bone metabolism in 32 untreated patients with lung cancer without metastasis. Materials and Methods: Patients underwent dual-energy X-ray osteodensitometry of proximal part of femoral bone. Osteopontin (OP), osteocalcin (OC) and alkaline phosphatase (AP) parameters were studied in blood, as well as osteo-associated chemical elements. Results: Lung cancer proceeds with severe disorders of bone metabolism, which is accompanied by an increase in blood levels of OP, OС, AP, phosphorus, lithium, lead, strontium and cobalt against a decrease of calcium, magnesium and manganese, which were observed in 75; 78; 31; 100; 66; 47; 44; 3; 100; 100, and 6% of patients, respectively; such disorder was associated with a morphological variant of the tumor (cobalt) and stage of disease (calcium, magnesium, manganese, strontium), development of osteodeficit (OP, OC, AR, strontium, zinc). Osteodeficit in the form of osteopenia and osteoporosis is observed more common in women, in every second patient, and osteodensimetric T-score depends on the age of patients, directly correlates with the values of the OP and OC, and inversely — with a zincemia rate. Conclusions: The disorders of bone metabolism in patients with lung cancer indicate the need for the development of antiosteoporosis treatment for cancer patients.
ANAGRELIDE AND THE CALR MUTATION ALLELE BURDEN IN ESSENTIAL THROMBOCYTHEMIA
Authors: Atkinson E , Bakri M , Hayat A , Langabeer S E
Published: January 2019

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ANALYSIS OF THE 3΄UTR REGION OF THE NOTCH1 GENE IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Authors: Abramenko I V , Bilous N I , Chumak A A , Dyagil I S , Martina Z V
Published: January 2019

Deregulation of NOTCH1-signalling pathway is common in chronic lymphocytic leukemia (CLL). The most of studies are focused on detection of the hotspot c.7541_7542delCT NOTCH1 mutations in exon 34, while studies of mutations in the 3′UTR region are rare. The aims of work were to evaluate the frequencies of mutations in the 3′UTR region of the NOTCH1 gene (9:136,495553-136,495994) in Ukrainian CLL patients, the distribution of rs3124591 genotypes located in that area, and association of NOTCH1 mutations with structure of B-cell receptor. Materials and Methods: Detection of mutations in the 3′UTR region of the NOTCH1 was performed by direct sequencing in 87 previously untreated CLL patients (from the total group of 237 CLL patients) with unmutated immunoglobulin heavy-chain variable (UM IGHV) genes and without mutations in hotspot regions of TP53, SF3B1, and exon 34 of NOTCH1 genes. Results: Mutations in the 3′UTR region of the NOTCH1 were revealed in three of 87 CLL patients (3.4%). Two cases with non-coding mutations were related to subset #1 of stereotyped B-cell receptors, and one case belonged to stereotyped subset #28a. Analysis with inclusion of 30 UM IGHV cases with previously detected c.7544_7545delCT mutations revealed that the frequency of UM IGHV genes of I phylogenetic clan (except IGHV1-69) was significantly increased, and the frequency of UM IGHV3 and IGHV4 genes, on the contrary, was reduced in NOTCH1-mutated cases comparing with NOTCH1-unmutated cases (p = 0.002) and the general group (p = 0.013). SNP rs3124591 did not affect the risk of CLL and survival parameters of the patients. At the same time, differences were found in the frequency of IGHV gene usage and in the structure of HCDR3 in carriers of individual genotypes. Conclusion: The frequency of NOTCH1 mutations in 3′UTR region was low. Our findings confirmed current data on the association between the structure of the B-cell receptor and the appearance of NOTCH1 mutations. Some features of HCDR3 structure were identified in carriers of TT and CC genotypes of rs3124591.
COMPARATIVE HISTOCHEMICAL EVALUATION OF MUCINS EXPRESSION IN FETAL ESOPHAGUS AND ADENOCARCINOMAS OF THE GASTROESOPHAGEAL JUNCTION
Authors: Vernygorodskyi S , Rekun T , Zhuchenko P
Published: January 2019

Aim: To study and compare the expression patterns of mucins in the fetal gastroesophageal junction (GEJ) region and adenocarcinomas of the GEJ in adults using histochemical method. Material and Methods: To reveal the expression of different mucins, tissue sections from formalin-fixed paraffin-embedded tissue blocks of fetal GEJ and carcinomas of GEJ were stained by the following histological stains: hematoxylin and eosin, periodic acid-Schiff (PAS), alcian blue (AB), pH 2.5, combined AB-PAS, and combined AB-Aldehyde Fuchsin (AB/AF). Results: Expression of mucins within the developing fetal GEJ has been demonstrated (gestational age 5–38 weeks). We studied histochemical features of neoplastic cells in carcinomas of GEJ from 90 adult patients. The results showed that in gastric type expression of neutral mucins dominated especially in well differentiated (G1) adenocarcinomas and corresponded to the last three months of GEJ development, while in the intestinal and mixed type significant acid mucins expression was detected in moderate (G2) and poorly (G3) differentiated adenocarcinomas and corresponded to 17–25 weeks of GA. No significant coincidence in mucins expression was observed in signet ring cell carcinomas in relation to GA. Conclusion: Our data suggest that decrease of neutral mucins level can be considered reliable phenotypic marker of poor prognosis of GEJ adenocarcinomas. Study of the developmental expression of mucin genes may improve understanding of the malignant transformation of esophageal tissue.
PARANEOPLASTIC SYNDROME IN LUNG CANCER
Authors: Dumansky Yu V , Syniachenko O V , Stepko P A , Yehudina Ye D , Stoliarova O Yu
Published: January 2019

Aim: To study the nature of different variants of paraneoplastic syndrome (PNPS) in lung cancer, taking into account the features of the tumorous process and the complications of radiochemotherapy. Patients and Methods: We performed an analysis of the data of 1,669 patients with lung cancer aged between 24 and 87 years, among whom there were 89% of men and 11% of women. The ratio of small cell and non-small-cell histological variants of the lung cancer was 1: 4, IB, IIA, IIB, IIIA, IIIB and IV stages of cancer — 1:2:6:58:43:57. Results: PNPS developed in 16% of the lung cancer patients, in these patients we have detected a marked increase in the disease incidence in women, the peripheral form of the tumor, the apical variant of Pancoast — Tobias and adenocarcinoma, but no cases of the median lower localization of the tumor. The number of the upper lobar pathology was decreased, while the severity of the cancer was significantly greater, which more often occurred with exudative pleurisy, germination of the tumor into the chest wall and compression of the upper vena cava. The 21 components of PNPS pathology were established. We distributed them conditionally into the musculoskeletal system lesions, variants of skin vasculitis and autoimmune processes, the nature of which depended on the localization and course of the tumorous process, its histological variation and severity of the course. Moreover, PNPS negatively affected the development of radiochemotherapy complications and worsened survival rate. Conclusions: The course of PNPS in lung cancer is highly diverse, being a risk factor for a severe tumorous process that worsens the survival of patients
ANALYSIS OF THE SURVIVAL OF PATIENTS WITH BREAST CANCER DEPENDING ON AGE, MOLECULAR SUBTYPE OF TUMOR AND METABOLIC SYNDROME
Authors: Grybach S M , Polishchuk L Z , Chekhun V F
Published: January 2019

Aim: To analyze the survival of patients with breast cancer (BC) depending on age, molecular subtype of the tumor and the presence of metabolic syndrome. Patients and Methods: We have analyzed the results of examination and treatment of 202 patients with BC of stages I–III. The patients were distributed by age into 2 groups. The group 1 included 86 elderly patients (from 65 to 84 years old), the group 2 — 116 younger patients (from 32 to 64 years). An overall 1-, 3- and 5-year survival rates of the treated patients were assessed. The significance of factors influencing the overall survival (OS) of patients with BC was determined using the methods of statistical analysis. Results: Molecular subtype of BC significantly affects survival rates: in a case of a luminal B subtype the 5-year OS was 71.6% vs 80% (p < 0.05) in groups 1 and 2, respectively while in a case of a basal-like subtype it was 60.2% and 71.6% (p < 0.05). The presence of metabolic syndrome significantly reduced the 5-year OS (up to 70.7% and 80.6%, p < 0.05 in groups 1 and 2, respectively). Conclusion: The OS is lower in elderly patients with BC compared with younger patients, especially in those who suffer from metabolic syndrome.
INFLUENCE OF FERROMAGNETIC NANOCOMPOSITE (FERROPLAT) ON HUMAN BREAST CANCER CELLS OF DIFFERENT MALIGNANCY DEGREES: PRO/ANTIOXIDANT BALANCE AND ENERGY METABOLISM
Authors: Chekhun V F , Todor I N , Lukianova N Yu , Gorbik D M , Lozovska Yu V , Burlaka A P , Borikun T V
Published: January 2019

Aim: To study the effect of Ferroplat (FrP) on the indexes of pro/antioxidant balance and energy metabolism in breast cancer cells of different malignancy degree and different sensitivity to drug therapy. Materials and Methods: The study was carried out on breast cancer cells of low (T47D, MCF-7) and high malignancy degree (MCF-7/DDP (cisplatin-resistant), MDA-MB-231, MDA-MB-468) using cell culture techniques, immunocytochemical, biochemical, biophysical methods, flow cytometry and polarography. Results: We established that the addition of FrP to the culture medium reduces the activity of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and the level of non-protein thiols by 32–41% (p < 0.05). At the same time, there was an increase of the total level of ROS and the rate of NO generation by inducible NO synthase by 1.7–2.5 times (p < 0.05). This testifies that FrP disturbs the antioxidant balance in cells, resulting in their death. Also, the use of FrP led to a decrease in the rate of oxygen absorption in MCF-7 and T47D cells by 26% and 25%, respectively (p < 0.05). In cells of high malignancy degree this index decreased by 38–40% under the influence of FrP. Incubation of MCF-7 and T47D cells with the indicated agent also reduced the content of phospholipid cardiolipin by 15–16% (p < 0.05), and in MDA-MB-231, MCF-7/DDP, MDA-MB-468 cells — by 29%, 30% and 32%, respectively. In addition, the effect of FrP caused a decrease in the levels of Mg2+ and lactate in MCF-7 and T47D cells by 21–29% and 14–24%, respectively, whereas in MDA-MB-231, MDA-MB-468, MCF-7/DDP cells — by 34–38% and 32–35%, respectively. In this case, the agent raised the level of glucose in the cells of low malignancy degree by 20–23% (p < 0.05), and in the cells of high malignancy degree and with the phenotype of drug resistance — by 31–36%. However, the nanocomposite did not affect the activity of lactate dehydrogenase in all studied breast cancer cells. Conclusion: The study has shown that FrP has an effect on the pro/antioxidant balance and energy metabolism of cancer cells. In addition, the denoted effect of FrP was more pronounced in the breast cancer cells with a high malignancy degree and the phenotype of drug resistance.
OXIDATIVE AND MUTAGENIC EFFECTS OF LOW INTENSITY GSM 1800 MHz MICROWAVE RADIATION
Authors: Yakymenko I , Burlaka A , Tsybulin O , Brieieva O , Buchynska L , Tsehmistrenko S , Chekhun V
Published: January 2019

Aim: Despite a significant number of epidemiological studies on potential carcinogenicity of microwave radiation (MWR) from wireless devices and a bulk of experimental studies on oxidative and mutagenic effects of low intensity MWR, the discussion on potential carcinogenicity of low intensity MWR is going on. This study aims to assess oxidative and mutagenic effects of low intensity MWR from a typical commercial model of a modern smartphone. Materials and Methods: The model of developing quail embryos has been used for the assessment of oxidative and mutagenic effects of Global System for Mobile communication (GSM) 1800 MHz MWR from a commercial model of smartphone. The embryos were exposed in ovo to 0.32 µW/cm2, discontinuously — 48 s — On, 12 s — Off, during 5 days before and 14 days through the incubation period. Results: The exposure of quail embryos before and during the incubation period to low intensity GSM 1800 MHz has resulted in expressive statistically significant oxidative effects in embryonic cells, including a 2-fold increase in superoxide generation rate and 85% increase in nitrogen oxide generation rate, damages of DNA integrity and oxidative damages of DNA (up to twice increased levels of 8-oxo-dG in cells of 1-day old chicks from the exposed embryos). Finally, the exposure resulted in a significant, almost twice, increase of embryo mortality. Conclusion: The exposure of model biological system to low intensity GSM 1800 MHz MWR resulted in significant oxidative and mutagenic effects in exposed cells, and thus should be recognized as a significant risk factor for living cells.
BER GENE POLYMORPHISMS ASSOCIATED WITH KEY MOLECULAR EVENTS IN BLADDER CANCER
Authors: Smal M P , Kuzhir T D , Savina N V , Nikitchenko N V , Rolevich A I , Krasny S A , Goncharova R I
Published: January 2019

Aim: Base excision repair (BER) gene polymorphisms are known to play an independent role in predisposition to developing different cancers as well as to be associated with clinicopathological traits of the disease modifying its clinical outcomes. One of the underlying mechanisms is presumed to include interplay between BER gene polymorphisms and key mutational, epigenetic and chromosomal events in tumor tissues. The present study was aimed at elucidating potential gene-gene interaction and assessing their mutual effects in bladder cancer (BC). Materials and Methods: The earlier obtained data on genotyping patients with verified diagnosis of BC for OGG1 rs1052133 (Ser326Cys) and XRCC1 rs25487 (Arg399Gln) polymorphisms were used for this study. The tumor tissue samples from the same patients were analyzed for mutations, epigenetic variations and losses of heterozygosity in some key genes involved in divergent pathogenic pathways of BC. Results: It was shown that the OGG1 (326 codon) heterozygous genotype as well as the minor 326Cys allele can intensify a mutational response of the RAS locus in urothelial carcinomas in the total cohort of patients simultaneously decreasing the mutation rates in the PIK3CA locus in smokers. The XRCC1 (399 codon) heterozygous genotype as well as the minor 399Gln allele reduced the frequency of LOH in the PTEN and TNKS genes, but did not affect the mutational variability in any locus tested. Both polymorphisms influenced the methylation status, carriers of OGG1 326Ser/Cys or Ser/Cys+Cys/Cys genotypes demonstrating increased frequency of methylated RUNX3 and ISL1 genes whereas the similar effect of XRCC1 polymorphism concerning methylation of p16 and TIMP3 genes. When dividing the total cohort into groups based on the extent of tumor spread, the observed associations were characteristic of non-muscle invasive BC. Conclusion: The BER gene polymorphisms contributed to modification of key molecular events in urothelial carcinomas. Their mutual effects mainly manifested in non-muscle invasive BC. The underlying mechanisms as well as possible clinical outcomes need to be further explored to propose novel prognostic biomarkers for BC.
OVEREXPRESSION OF THE MITOCHONDRIAL RIBOSOMAL PROTEIN S18-2 IN THE INVASIVE BREAST CARCINOMAS
Authors: Buchynska L G , Iurchenko N P , Kashuba E V , Brieieva O M , Glushchenko N M , Mints M , Lukianova N Yu , Chekhun V F
Published: January 2019

Background: Recent studies allow to consider the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) as a potential oncoprotein, which suggests the need for further characterization of its expression in tumors of different genesis including breast cancer (BC). The aim of the study was to analyze the expression of the S18-2 protein in BC of luminal A and basal subtypes. Materials and Methods: Operational material of BC patients stage І–ІІ (luminal A subtype, n = 30, and basal subtype, n = 10) was studied with the use of morphological, immunohistochemical, statistical and bioinformatic methods. Results: Using the immunohistochemical analysis, we found that the S18-2 protein showed the nuclear signal in 66.7% of luminal A subtype BC samples and 80.0% of basal subtype BC samples. The variability of the S18-2 expression in both the luminal A and basal subtypes of BC was revealed. Noteworthy, the number of cells expressing S18-2 in high-proliferating tumors of luminal A and basal subtype is significantly higher than in tumors with a low proliferative potential (p < 0.05). In 10 samples of luminal A subtype, the nuclear S18-2 signal was higher than median value. Moreover, the S18-2 protein was overexpressed in 4 out of such 10 samples. Metastases in the lymph nodes were found in 3 out of 4 patients with the stage II BC, low differentiation grade of the tumor and high proliferative activity. The bioinformatic analysis confirms our preliminary findings that the trend for increasing expression of the S18-2 protein in tumors correlates with the aggressiveness of malignant BC. Conclusion: The S18-2 protein may be a marker of cancer aggressiveness in BC patients.
FOXP3 GENE POLYMORPHISM IS ASSOCIATED WITH BREAST CANCER IN IRANIAN PATIENTS
Authors: Arabpour F , Shafizad A , Rahimzadeh M , Norouzian M , Naderi N
Published: January 2019

Aim: Breast cancer (BC) is one of the leading causes of cancer death among women. Recent studies have characterized FoxP3 as a marker of regulatory T cells and an X-linked tumor suppressor gene, which is involved in the pathogenesis of BC. Therefore, we investigated the potential influence of three single-nucleotide polymorphisms (SNPs) of FoxP3 gene on the development of BC in Iranian women. Materials and Methods: The association between FoxP3 rs2232365, rs3761548 and rs4824747 polymorphisms and BC risk was assessed in 124 BC patients and 198 healthy controls using sequence-specific primers. Results: We identified significant difference of rs3761548 in both allele and genotype frequencies between cases and control groups. Our results showed that individuals carrying FoxP3 rs3761548 AA genotype had about 4.3-fold increased risk of BC compared with CC carriers. No significant association was found between rs3761548C>A polymorphism and clinical outcome parameters (age of onset, tumor size, lymph nodes metastasis, tumor stage, progesterone receptor status, estrogen receptor status, Ki-67 status, HER-2 status and duration of disease). Conclusion: This study has provided the first genetic data on the FoxP3 gene polymorphism in south of Iran and proposes the rs3761548 polymorphism of FoxP3 gene as a risk factor, but not a prognostic marker in the development of BC in Iranian population.
PROFESSOR VOLODYMYR OLEKSIIOVYCH SHLYAKHOVENKO (on the 80th birth anniversary)
Authors: Board Editorial
Published: January 2019

The studies by Prof. V. Shlyakhovenko are always on the front edge of the science. And nowadays he focuses on the search for the markers of tumor growth and monitoring of cancer treatment.
EXPANDING FRUIT PRODUCT MARKET THROUGH BRAND, SALES AND DISTRIBUTION CHANNEL AND PRODUCT QUALITY
Authors: Do Duc Kha , Anh Tuan Nguyen , Pham Duc Chinh , Thanh Tu Huynh
Published: January 2019

This paper focuses on determining three basic factors affecting the capture of market share and expansion of the fruit product market, namely brand, sales and distribution channel and product quality. We seek to answer if there is a significant difference between fruit products which are of high quality, well-branded, distributed and sold through an established system and those without. If yes, whether it can be measured. To find out the difference, we compared prices of fruit products of strong brands and sold in an established sales and distribution system and similar fruit products without brand and sales and distribution system. To measure the impact of these three factors on the possibility in capturing market share of the products, we employed Structural Equation Modeling (SEM). The Confirmatory Factor Analysis (CFA) is utilized to inspect the extent that each factor affects the expansion of fruit product consuming market, thereby evaluating the situation and proposing solutions. Quantitative data is obtained from fruit producers in Long An, Tien Giang, Vinh Long, Ben Tre, Can Tho, Hau Giang, and Dong Thap as well as from consumers in provinces and Ho Chi Minh City in the period from October to December, 2013.
Implementation of Mind Mapping Learning Model to Improve English Learning Outcomes in Simple Descriptive Texts
Authors: Junaedy Junaedy
Published: January 2019

Writing is a linguistic activity that plays an important role in the dynamics ofhuman civilization. Through writing activities, people can also benefit for theirdevelopment. Unfortunately, English lessons at Ambulu 2 Junior High Schoolshowed indications of a decline. This is a classroom action research that aimedto find out how the implementation of mind mapping learning models canimprove English achievement of the seventh grade students of Class VII-C atSMPN 2 Ambulu. The results showed that learning with the Mind Mappingmodel had a positive impact in improving student learning outcomes whichwas marked by an increase in student’s achievement in each cycle, that is cycleI (61.76%), cycle II (76.47%), cycle III ( 94.12%). Likewise, the application ofthe Mind Mapping model can improve student learning activities as indicatedby the score of observations showing an increase in the percentage of studentactivity, that is cycle I (23.53%), cycle II (73.53%) and cycle III (91.18). This means that the mind mapping learning model is good to be applied in teaching andlearning activities in English materials for Preparing Simple Descriptive Texts.
Methyl Vanillate Ether Derivatives as Future Potential Drug
Authors: Satpute Maruti S. , Gangan Vijay D. , Shastri Indu
Published: January 2019

Vanillic acid (4-hydroxy-3-methoxybenzoic acid) is a dihydroxybenzoic acid derivative used as a flavouring agent. It is used in the synthesis of various active pharmaceutical ingredients such as Etamivan, Modecainide, Brovanexine, Vanitiolide, Vanyldisulfamide etc. In this paper, novel ether derivatives of vanillic acid were synthesized and tested for potential antibacterial activity. This combinatorial synthesis of novel vanillic acid ether derivatives can be a useful approach to generate potent chemotherapeutic agents in developing new drug candidates.
用爱构建和谐的师生关系
Authors: 吴 凤丽
Published: January 2019

教育学生要不断更新自己的思想观念,丰富自己的头脑,不断地学习,努力提升自己的综合素质。教育要以爱字当头,才能构建良好的师生关系。因此,做一名优秀的人民教师,树立以德施爱的教育理念,是教育的关键。
如何使小学数学课堂教育回归自然
Authors: 吴 成会
Published: January 2019

新课程改革以来,数学教学在教学内容与教学方式上都有了翻天覆地的变化,详实的多维目标,形式多样的教学设计,动静结合的多媒体设计,热闹异常的小组合作、小组讨论以及我们的公开课、展示课、评优课大抵如此。这些课看似精彩纷呈,但是细细品来,有些“变质”“变味”,并没有真正贯彻课改精神,与真正的有效课堂、本真的数学课堂渐行渐远。作为一线教师,我们应该追求真实、自然的数学课堂,多站在学生的角度来考虑。真实、自然绝不是简单、单一,而是教学的一种更高境界,它折射出老师的精湛的教学艺术、深刻的教学思想,它更能彰显教育者的智慧。
浅析高职学生法律意识培养问题
Authors: 罗 超凡
Published: January 2019

全面依法治国战略的提出,给大学生的法治教育提出了更高更具体的要求,同时,也为大学生的法治教育带来了新的研究方向和新的研究课题。本文从高职学生的法律意识现状出发,探讨法律意识培养的具体内容,从而提出加强他们法律意识的方法。
APLIKASI PENCARIAN LOKASI PANTI ASUHAN DI KOTA AMBON BERBASIS MOBILE
Authors: Irawati Irawati , Aswin Hafiza , Salim Yulita
Published: January 2019

The diverse population of Ambon City has led to a diversity of spiritual beliefs that can be found in this city, this also has an impact on the orphanages built in Ambon City. Based on the source www.malukuprov.go.id, which is the official address of the Ambon City Government website, there is no information relating to the orphanage. As a result, donors in Ambon City experienced difficulties in getting accurate information about orphanages, because limited information from prospective donors took the initiative by asking the public to obtain information about the local orphanage. The location search application for this orphanage was built using the Location Based Service (LBS) system that can provide information on routes to orphanages to donors through mobile android users equipped with navigation features and display information about the related orphanage to facilitate donors in concluding the orphanage which ones need more donations.
Í minningu Jakobínu
Authors: Hólmgeirsdóttir Jóna Kristjana , Pálsdóttir Karítas Hrundar
Published: January 2019

Sögurnar og ljóðin sem hér birtast, eftir þær Jónu Kristjönu Hólmgeirsdóttur og Karítas Hrundar Pálsdóttur ritlistarnema, voru samin undir áhrifum frá Jakobínu Sigurðardóttur sem hefði átt aldarafmæli árið 2018.
„Hún reyndi ekki að kalla á hjálp...“
Authors: Sæmundsdóttir Þórhildur , Einarsdóttir Þorgerður J.
Published: January 2019

The paper analyzes the rulings of the Supreme Court of iceland in rape cases after changes in the penal code in 1992 and 2007. The study employs discourse analysis in which legitimizing principles are identified. The aim of the paper is to explore whether victim blaming, misogyny or other such attitudes are reflected in the rul­ings. The paper concludes that the rulings’ focus is mainly on physical abuse and violence although less emphasis is put on that after the changes in the penal code. Mental harm caused by rape is often given little attention or even completely igno­red. One main conclusion is that rape myths are reflected in the rulings and victim blaming is common although it is decreasing. it is also apparent that the emphasis on victim blaming diminishes if the perpetrator is of foreign origin.
Gleðimenn, gleðimeyjar og Gleðikvennafélag Vallahrepps
Authors: Þórhallsdóttir Guðrún
Published: January 2019

This paper discusses the history of the nouns gleðimaður, which is known from Old as well as Modern icelandic, and gleðikona which first occurs in an 18th-century source. Other nominal compounds for men and women that have gleði- as their first member are also introduced. The meaning of these words is compared, as is their usage, in order to test the claim that the words for men normally have a neutral meaning (‘cheerful man, party animal’) but the words for women have a pejorative meaning (‘hussy, prostitute’). The nature of the changes in the history of the gleði-compounds is also discussed, e.g., to what extent borrowing from a foreign language has taken place. Lars-Gunnar Andersson’s categorization of the so-called “ugliness” of words is used for a more detailed definition of the semantic changes. Finally, we touch on the wish to reclaim the word gleðikona that has been observed in the last decades, i.e., to revive the practically forgotten meaning ‘cheerful woman, female party animal’.