bluuebunny/crossref_metadata_2025 huggingface dataset:
CIRCULATING TUMOR CELLS IN BREAST CANCER: FUNCTIONAL HETEROGENEITY, PATHOGENETIC AND CLINICAL ASPECTS
Authors: Cherdyntseva N V , Litviakov N V , Denisov E V , Gervas P A , Cherdyntsev E S
Published: January 2019

Each patient has a unique history of cancer ecosystem development, resulting in intratumor heterogeneity. In order to effectively kill the tumor cells by chemotherapy, dynamic monitoring of driver molecular alterations is necessary to detect the markers for acquired drug resistance and find the new therapeutic targets. To perform the therapeutic monitoring, frequent tumor biopsy is needed, but it is not always possible due to small tumor size or its regression during the therapy or tumor inaccessibility in advanced cancer patients. Liquid biopsy appears to be a promising approach to overcome this problem, providing the testing of circulating tumor cells (CTC) and/or tumor-specific circulating nucleic acids. Their genomic characteristics make it possible to assess the clonal dynamics of tumors, comparing it with the clinical course and identification of driver mutation that confer resistance to therapy. The main attention in this review is paid to CTC. The biological behavior of the tumor is determined by specific cancerpromoting molecular and genetic alterations of tumor cells, and by the peculiarities of their interactions with the microenvironment that can result in the presence of wide spectrum of circulating tumor clones with various properties and potentialities to contribute to tumor progression and response to chemotherapy and prognostic value. Indeed, data on prognostic or predictive value of CTC are rather contradictory, because there is still no standard method of CTC identification, represented by different populations manifesting various biological behavior as well as different potency to metastasis. Circulating clasters of CTC appear to have essentially greater ability to metastasize in comparison with single CTC, as well as strong association with worse prognosis and chemoresistance in breast cancer patients. The Food and Drug Administration (USA) has approved the CTC-based prognostic test for clinical application in patients with advanced breast cancer. Prospective clinical trials have demonstrated that measuring changes in CTC numbers during treatment is useful for monitoring therapy response in breast cancer patients. Molecular and genetic analysis of CTC gives the opportunity to have timely information on emergence of resistant tumor clones and may shed light on the new targets for pathogenetic antitumor therapy.
ANTI-HISTONE H1 IgGs POSSESS PROLIFERATIVE ACTIVITY TOWARDS HUMAN T-LEUKAEMIA CEM CELLS
Authors: Kit Yu , Magorivska I , Bilyi R , Myronovskij S , Stoika R
Published: January 2019

The aim of this study was to characterize the proliferative activity of the anti-histone H1 IgGs towards human T-leukaemia CEM cells. Materials and Methods: Anti-histone H1 IgGs were purified from blood serum of systemic lupus erythematosus patients by precipitation of serum proteins with 50% ammonium sulfate followed by a sequential affinity chromatography on Protein GSepharose and histone H1-Sepharose columns. To avoid contamination with other proteins, anti-histone H1 IgGs were subjected to strongly acidic pH 2.0 during gel filtration through HPLC column. The effects of the anti-histone H1 IgGs on cell viability and cell cycle were tested by MTS-assay and flow cytometry, correspondingly. The cross-reactivity of the anti-histone H1 antibodies towards heterogenetic and cellular antigens was evaluated by Western-blot analysis. Results: It was found that incubation of CEM cells with the HPLC-purified anti-histone H1 IgGs resulted in significant stimulation of cell growth by 46% after 48 h of incubation. These IgGs possess an antigenic poly-specificity to positively charged heterogenetic antigens and different cellular antigens. FITC-labeled and biotinylated anti-histone H1 IgGs are internalized by CEM cells and preferentially accumulated in the cytoplasm. Conclusion: The anti-histone H1 IgGs are shown to internalize human T-leukemia CEM and stimulate their proliferation. These IgGs are polyspecific toward cellular antigens.
ANTICANCER EFFECT AND IMMUNOLOGIC RESPONSE TO XENOGENEIC EMBRYONIC PROTEINS IN MICE BEARING EHRLICH SOLID CARCINOMA
Authors: Symchych T V , Fedosova N I , Karaman O M , Yevstratieva L M , Voeykova I M , Potebnya H P
Published: January 2019

Aim: To investigate anticancer and immunologic effects of chicken embryonic proteins (CEP) in mice bearing Ehrlich solid carcinoma. Materials and Methods: The study was carried out on male Balb/c mice bearing Ehrlich solid carcinoma. The immunizations were performed after the tumor transplantation. The immune status was assessed on days 7, 14, 21 and 28 after the tumor challenge. Cytotoxic activity (CAT) of macrophages (Mph), natural killer cells (NK), cytotoxic T-lymphocytes (CTL) and blood serum, as well as the influence of the blood serum on immune cells activity was checked in MTT-assay; Mph’s cytochemical activity was tested in NBT-assay; Ehrlich antigen-specific or CEP-specific antibodies were detected in ELISA-assay; medium size circulating immune complexes (CIC) were detected in reaction of 4.5% polyethylene glycol precipitation. Results: The immunization resulted in tumor growth suppression and significant 25.64% prolongation of the survival time. In both control and immunized mice with transplanted tumors antibodies specific to Ehrlich carcinoma antigens and to CEP were detected, but antibody response was more balanced in the treatment group. In the treatment group both cytochemical and CAT of Mph was moderately activated and well preserved until late stages of tumor development; CAT of NK and CTL remained in the range of the intact mice until day 28 after the tumor transplantation. The immunized mice were well protected from accumulation of CIC and suppressive activity of autologous blood serum. Conclusion: Collectively, our data indicate that CEP can elicit immunomodulating and immunoprotecting effects sufficient to provide tumor growth inhibition. The further elaboration of a xenogeneic anticancer vaccine based on CEP is warranted.
IMPACT OF LACTIC ACIDOSIS ON THE SURVIVAL OF LEWIS LUNG CARCINOMA CELLS
Authors: Kolesnik D L , Pyaskovskaya O N , Solyanik G I
Published: January 2019

Aim: To investigate the effect of lactic acidosis on the survival of Lewis lung carcinoma cells under glucose-deprived conditions. Materials and Methods: LLC/R9 variant of Lewis lung carcinoma cells was cultured in glucose deficit or complete culture medium. Conditions of lactic acidosis, lactosis, and acidosis were generated in glucose deficit medium. Cell survival, cell cycle, apoptosis, autophagy, and the content of glucose, lactate, vascular endothelial growth factor in the culture medium were determined. Light and fluorescent microscopy, flow cytometry, spectrophotometry, and ELISA were used. Results: It has been found that 24 h incubation of tumor cells under lactic acidosis caused (i) the reduction of the number of living cells by 33% (p < 0.05) and 56% (p < 0.05); (ii) the inhibition of apoptosis by 4.3-fold (p < 0.05) and 3.3-fold (p < 0.05); (iii) the reduction of the rate of glucose consumption by 2-fold (p < 0.05) and 2.5-fold (p < 0.05); (iv) an increase of lactate production more than twice (p < 0.05) and 1.6-fold (p < 0.05) compared with these indexes under conditions of glucose deficiency or complete glucose-containing medium, respectively. However, on the second day of culture under lactic acidosis, the number of viable cells reached a maximum, in contrast to culture in the complete medium. The number of live cells on the seventh day of culture under lactic acidosis exceeded almost 2–3 times (p < 0.05) that in the culture under conditions of the glucose deprivation or in complete medium. On the third day under lactic acidosis the autophagolysosomes count was 54% (p < 0.05) lower that that under glucose deficit. Conclusions: Lactic acidosis promoted the survival and proliferation of Lewis lung carcinoma cells by energy system reprogramming directed on inhibition of apoptosis and autophagy, a significant decrease in the rate of glucose utilization and activation of glutaminolysis and, consequently, increase of the lactate production rate. Inhibition of lactate production by tumor cells may be considered as a promising approach for more efficient antiangiogenic treatment of cancer.
COMPARISON OF CHROMOSOMAL REARRANGEMENTS IN BONE MARROW CELLS AND BLAST TRANSFORMED B-CELLS IN RELAPSE OF B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA/ SMALL LYMPHOCYTIC LYMPHOMA
Authors: Andreieva S V , Korets K V , Ruzhinska O E , Skorokhod I M , Alkhimova O G
Published: January 2019

Aim: The genetic mechanisms of resistance to chemotherapy in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) are not clear. We aimed to determine the peculiarities of abnormal karyotype formation in bone marrow (BM) cells and peripheral blood (PB) blast transformed B-cells in relapse of B-CLL/SLL. Materials and Methods: Cytogenetic GTG banding technique and molecular cytogenetic in interphase cells (i-FISH) studies of BM cells and PB blast transformed B-lymphocytes were performed in 14 patients (10 males and 4 females) with B-CLL/SLL. Results: The results of karyotyping BM and PB cells revealed the heterogeneity of cytogenetic abnormalities in combined single nosological group of B-CLL/SLL. In PB B-cells, chromosome abnormalities related to a poor prognosis group were registered 2.5 times more often than in BM cells. Additional near tetraploid clones that occurred in 57.1% cases were the peculiar feature of BM cell karyotypes. Chromosomal rearrangements characteristic of the group of adverse cytogenetic prognosis were revealed in all cases from which in 2 cases by karyotyping BM cells, in 6 cases in PB B-cells and in 8 cases by the i-FISH method in BM cells, i.e. their detection frequency was 3 times higher in PB B-cells and 4 times higher when analyzing by i-FISH in BM cells. Conclusions: Mismatch in abnormal karyotypes in BM and PB B-cells by the presence of quantitative and structural chromosomal rearrangements may be indicative of simultaneous and independent processes of abnormal clone formation in the lymph nodes and BM hematopoietic cells. Accumulation the information about previously unidentified chromosomal rearrangements in relapse of the disease may help to understand the ways of resistance formation to chemotherapy.
GENOME-WIDE ASSOCIATION STUDY OF LOSS OF HETEROZYGOSITY AND METASTASIS-FREE SURVIVAL IN BREAST CANCER PATIENTS
Authors: Deryusheva I V , Tsygano M M , Garbukov E Y , Ibragimova M K , Kzhyshkovska Ju G , Slonimskaya E M , Cherdyntseva N V , Litviakov N V
Published: January 2019

One of the factors providing the diversity and heterogeneity of malignant tumors, particularly breast cancer, are genetic variations, due to gene polymorphism, and, especially, the phenomenon of loss of heterozygosity (LOH). It has been shown that LOH in some genes could be a good prognostic marker. Aim: To perform genome-wide study on LOH in association with metastasisfree survival in breast cancer. Materials and Methods: The study involved 68 patients with breast cancer. LOH status was detected by microarray analysis, using a high density DNA-chip CytoScanTM HD Array (Affymetrix, USA). The Chromosome Analysis Suite 3.1 (Affymetrix, USA) software was used for result processing. Results: 13,815 genes were examined, in order to detect LOH. The frequency of LOH varied from 0% to 63%. The association analysis identified four genes: EDA2R, PGK1, TAF9B and CYSLTR1 that demonstrated the presence of LOH associated with metastasis-free survival (log-rank test, p < 0.03). Conclusions: The presence of LOH in EDA2R, TAF9B, and CYSLTR1 genes is associated with metastasis-free survival in breast cancer patients, indicating their potential value as prognostic markers.
STRESS DURING PUBERTY FACILITATES PRECANCEROUS PROSTATE LESIONS IN ADULT RATS
Authors: Herrera-Covarrubias D , Coria-Avila G A , Hernandez M E , Ismail N
Published: January 2019

Puberty can be a critical period for the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. Some organs like the prostate are prone to diseases that result from neuroendocrine or immune challenges, such as cancer. Aim: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) on the development of precancerous lesions in adult rats, and compared them with testosterone-induced prostatic lesions. Materials and Methods: Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5 weeks old). At adulthood (8 weeks old) males were subcutaneously implanted with either an empty capsule or filled with testosterone propionate (100 mg/kg). This resulted in a total of five groups: 1) intact untreated, 2) saline-treated and implanted with a blank capsule, 3) saline-treated and implanted with a testosterone capsule, 4) LPS-treated and implanted with a blank capsule, 5) LPS-treated and implanted with a testosterone capsule. Four weeks later, the rats were sacrified and their prostates processed for histology (hematoxylin and eosin stain) and blood serum processed for hormone analysis (testosterone and corticosterone). Results: Males treated with LPS (stressed during puberty via immune challenge) expressed epithelium dysplasia (specially in the ventral prostate), anisocytosis, presence of mononuclear cells, anisokariosis, non-basal polarity, abnormal nucleus-cytoplasm ratio, proplastic myoepithelium, and granular content in the lumen. These histological alterations were similar, but less severe than those observed in males implanted with testosterone during adulthood. Conclusion: These results indicate that pubertal exposure to an immune challenge (stress) facilitates the long-term development of prostatic lesions in adult male rats.
CD150 AND CD180 ARE INVOLVED IN REGULATION OF TRANSCRIPTION FACTORS EXPRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA CELLS
Authors: Gordienko I M , Shlapatska L M , Kholodniuk V M , Kovalevska L M , Ivanivskaya T S , Sidorenko S P
Published: January 2019

Background: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression. From other side we attempted to regulate TFs expression via CD150 and CD180 cell surface receptors. Materials and Methods: Studies were performed on normal peripheral blood B-cell subpopulations and chronic lymphocytic leukemia (CLL) cells isolated from peripheral blood of 67 primary untreated patients with CLL. Evaluation of TFs expression was performed on mRNA level using qRT-PCR and on protein level by western blot analysis. Results: Median of PAX5 and EBF1 mRNA expression was higher in cell surface CD150 positive (csCD150+) compared to csCD150- CLL cases or normal CD19+ and CD19+CD5+ B-cell subsets. Differences in mRNA expression of IRF8, IRF4 and BLIMP1 between studied groups of CLL and normal B cells were not revealed. All CLL cases were characterized by downregulated expression of PU.1 and BCL6 mRNAs in comparison to normal B cells. At the same time elevated SPIB mRNA expression level was restricted to CLL cells. Protein expression of IRF4, IRF8 and BCL6 was uniformly distributed between csCD150- and csCD150+ CLL cases. PU.1 protein and CD20 that is direct PU.1 target gene positively correlated with CD150 cell surface expression on CLL cells. Ligation of CD150 and CD180 alone or in combination upregulated IRF8 and PU.1 while downregulated the IRF4 mRNA expression. Signaling via CD150 or CD180 alone elevated the level of BCL6 mRNA. Strong downregulation of IRF4 mRNA was observed after CD150, CD180 or CD150 and CD180 coligation on CLL cells. We found that in CLL cells CD150 is a negative regulator of SPIB while CD180 is involved in upregulation of EBF1 expression level. Moreover, CD180 ligation on CLL cells caused increase of CD150 mRNA level that is a one of the EBF1 target genes. Conclusions: Analysis of TFs expression profile revealed upregulated SPIB mRNA level and downregulated PU.1 in CLL cells. CD150 and CD180 receptors may modulate transcriptional program in CLL cells by regulating the TFs expression levels.
VOLODYMYR SERHIIOVYCH MOSIIENKO (1934–2017)
Authors: Board Editorial
Published: January 2019

Professor Volodymyr Serhiiovych Mosiienko, the scientist, the leading researcher, Doctor of Medicine passed away
CHARACTERIZATION OF THE CYTOTOXIC EFFECTS OF THE COMBINATION OF CISPLATIN AND FLAVANOL (-)-EPICATECHIN ON HUMAN LUNG CANCER CELL LINE A549. AN ISOBOLOGRAPHIC APPROACH
Authors: Varela-Castillo O , Cordero P , Gutiérrez-Iglesias G , Palma I , Rubio-Gayosso I , Meaney E , Ramirez-Sanchez I , Villarreal F , Ceballos G , Najera N
Published: January 2019

Background: Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added simultaneously with cisplatin. Materials and Methods: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed. Results: We found that epicatechin has a concentration-dependent inhibitory effect on proliferation of tumor cells and the isobolographic analysis reveals that the effect of its combination with cisplatin is synergistic. It was also observed that epicatechin promotes cell death by apoptosis. Conclusions: Epicatechin might be considered for future studies to explore its possible use as coadjuvant in cisplatin-based treatments.
THE ANALYSIS OF METHYLATION OF DNA PROMOTER OF SFRP2 GENE IN PATIENTS WITH HYPERPLASTIC PROCESSES OF THE ENDOMETRIUM
Authors: Marichereda V G , Bykovа N A , Bubnov V V , Manasova G S , Moskalenko T Y , Volyanska A G , Shevchenko I M , Adamovska T M
Published: January 2019

The hyperplastic processes of the endometrium can arise not only against the background of excessive influence of estrogen, but also against the background of epigenetic damages that affect apoptosis, cell proliferation, differentiation, and adhesion, and DNA reparation. The aim of our study was to investigate and analyze the status of methylation of the promoter of SFRP2 gene in patients with hyperplastic processes of the endometrium. Materials and Methods: The study groups were the following: I — patients with endometrial hyperplasia (EH, n = 9); II — patients with endometrial intraepithelial neoplasia (EIN, n = 10), III — control groups: 1) with endometrial cancer (EC, n = 4), and 2) healthy women (n = 4). Determination of promoter methylation of SFRP2 gene was carried out by the semiquantitative method of methylation-specific PCR assay. Results: The maximum level of methylation of SFRP2 gene promoter had been revealed in patients with EC — 42.80 ± 3.55% (р < 0.05). The patients of the I group had the lowest values of methylation of SFRP2 gene promoter — 10.66 ± 0.85%, while in patients of the II group this indicator was higher — 20.60 ± 0.95% (р < 0.05). In healthy women of the control group, methylation of SFRP2 gene promoter was detected in none of the samples. Conclusion: The content of the methylated SFRP2 gene in endometrial tissue of patients with hyperplastic processes higher than 20–25% allows relate these women to the risk group of EC development and dictates the need of intensive observation of such patients.
LYMPHOCYTE COUNT IN PERIPHERAL BLOOD IS A SENSITIVE TOOL IN PRETREATMENT ASSESSMENT OF PATIENTS WITH UROLOGICAL
Authors: Yakovlev P , Klyushin D
Published: January 2019

Cancer, inflammation and immune surveillance recruit lymphocytes as common key cellular players. The aim of the study was to assess a utility of the absolute and relative lymphocyte counts (ALC and RLC) in peripheral blood of patients with urological cancer as sensitive tool in pretreatment assessment of patient, which correlates with postoperative outcome of the disease, and outlines the overall reactivity of the patient. Materials and Methods: We retrospectively studied correlation between lymphocyte count in peripheral blood of the patients with urological cancer (n = 789) and number of clinical parameters: cancer localization, stage of the disease, treatment outcome, complications. Mann — Whitney two-tailed test and logistic regression models were used. Results: Lymphocyte counts (both absolute and relative) correlate with the cancer stage, and status of the disease, allowing differentiate patients with urological cancer, from healthy individuals, and from the cancer patients after radical surgery. In patients with kidney and bladder cancer, lymphocyte count allowed differentiate the stages of the disease. Lower rate of the reactivity of the patient to the cancer treatment is accurately predicted by the ALC and RLC: those in highest quartile for lymphocytes count have shorter postoperative recovery. Patients in lowest quartile demonstrated worst postoperative performance, including cases of early postoperative mortality due to weak somatic status. Conclusion: The study presents evidence that pretreatment lymphocyte count in the peripheral blood of patients with urological cancer is a sensitive marker of cancer stage, and the reactivity of the patient to the cancer treatment, which can be used in the pretreatment assessment of the patient.
CLINICAL AND IMMUNOHISTOCHEMICAL FEATURES OF PRIMARY BREAST CANCER AND METACHRONOUS OVARIAN AND ENDOMETRIAL TUMORS
Authors: Kryzhanivska A E , Dyakiv I B , Kyshakevych I
Published: January 2019

The aim of the study was to assess the patterns of development of metachronous cancer (endometrial cancer, EC, and ovarian cancer, OC) in breast cancer (BC) patients dependent of receptor phenotype of breast tumors. Materials and Methods: In the study, 63 patients with ВС, who developed metachronous EC (n = 47) or OC (n = 16) were enrolled. Expression of estrogen receptor (ER), progesterone receptor (PR), HER/2neu was assessed using immunohistochemical approach. Results: BC in patients with metachronous EC and OC was characterized by a different frequency of molecular subtypes with the dominance of luminal A (36%) and B (43%) subtypes. In primary BC, we have established a correlation between ER expression and regional lymph nodes status (r = −0.50, p < 0.05); negative correlation between HER2/neu expression and tumor stage (r = −0.48, p < 0.05); between the molecular subtype of BC and its size (r = −0.33, p <0.05), the molecular subtype of primary BC and metastases in regional lymph nodes (r = 0.27, p <0.05). In the patients with luminal subtype BC metachronous tumors developed with the highest frequency (OC — 50%, EC — 50%). After treatment of primary BC metachronous tumors developed at different period: EC (22.2%) — most often in 3–5 years, OC (11.0%) — after 10 years and more. Conclusion: Our data evidence on the clinical significance of the individual characteristics of the BC, especially its molecular subtype, and the need to calculate the personalized risk of development of metachronous tumors of the reproductive system in patients with the BC.
INTERSECTION BETWEEN GENES CONTROLLING VASCULARIZATION AND ANGIOGENESIS IN RENAL CELL CARCINOMAS
Authors: Souchelnytskyi S
Published: January 2019

Aim: To show that application of the systemic analysis may significantly improve comparison of different datasets. Different genes and proteins may converge on the same functional outputs. A comparison of 2 datasets by only identification names of affected molecules may miss that, leading to a conclusion that there is nothing in common for these datasets. Systemic analysis may overcome this limitation, by focusing on functions represented by the identification names. Materials and Methods: Datasets were retrieved from open sources. Systemic analysis of vascularization features and angiogenesis signature was performed by using Cytoscape and its plugs-in. Results: In contrary to the initial statement of the lack of overlap between the vascularization features and the angiogenesis genes-signature in renal carcinomas, we observed an intersection on the functional level. Analysis of the networks built with identification names of vascularization and angiogenesis datasets showed an intersection, which included potent regulators of vessel formation and growth. Conclusion: Analysis of networks may expose functional links, which may be missed by a direct identification names comparison.
CLINICAL CASE OF A PATIENT UNDERGOING RADIUM-223 TREATMENT FOLLOWING TREATMENT WITH ABIRATERONE ACETATE AND ENZALUTAMIDE
Authors: Jimenez Romero M E , Diez Farto S , Navarro Serrato J C , Canelon Castillo E , Revelo Cadena I
Published: January 2019

Objective: Over the last decade, significant advances have been made in the development of therapies for patients with metastatic castration-resistant prostate cancer. Abiraterone and enzalutamide were approved as treatments based on data supporting improved overall survival compared to placebo. Radium-223 became the first approved radiopharmaceutical which decreased skeletal-related events, palliated pain, and showed improved overall survival in symptomatic patients with castration-resistant prostate cancer and bone metastasis only. Materials and Methods: We present the case of an eighty-two year old man with metastatic castrationresistant prostate cancer who was treated with sequential therapy (abiraterone — enzalutamide — radium 223). The sequencing and treatment used for our patient was viable because of his clinical characteristics, which have allowed for longer survival time with an acceptable quality of life. These actions must be agreed on by the Multidisciplinary Tumour Board, in order to optimize the use of available courses of treatment. Results: The treatment of these patients is changing rapidly, but many questions remain regarding the optimal sequencing of the available drugs. Sequential or concomitant use of the next generation hormonal agents — abiraterone and enzalutamide — cannot currently be recommended. Data regarding the safety of concomitant abiraterone, enzalutamide or denosumab with radium-223 is reassuring and timely. However, we cannot advocate the general use of combined radium-223 therapy at this time, irrespective of prior therapy. Conclusion: A better understanding of active mechanisms, the genetic characteristics of each metastatic castration-resistant prostate cancer and the development of new prognostic and predictive biomarkers will help determine sequencing or different combination treatments for each individual patient.
MATERIALS OF SYMPOSIUM AND SUMMER SCHOOL “FUNDAMENTAL PRINCIPLES OF CANCER BIOTHERAPY”, MAY 21–23, 2018, KYIV, UKRAINE
Authors: Board Editorial
Published: January 2019

The International Scientific Symposium “Fundamental Principles of Cancer Biotherapy” was held on May 21–23, 2018 in Kyiv, Ukraine. It was organized by R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology (IEPOR) of the National Academy of Sciences of Ukraine (NASU). The symposium was supported by the VACTRAIN project (TWINNING on DNA­based Cancer Vaccines, No 692293) in the frame of the European Union’s Horizon 2020 Research and Innovation Program.
EFFECT OF VALPROIC ACID IN COMPARISON WITH VORINOSTAT ON CELL GROWTH INHIBITION AND APOPTOSIS INDUCTION IN THE HUMAN COLON CANCER SW48 CELLS IN VITRO
Authors: Sanaei M , Kavoosi F , Mansoori O
Published: January 2019

Aim: Acetylation levels of histones are the result of the balance between histone acetyltransfrases and histone deacetylases activities, which plays an important role in chromatin remodeling and regulation of gene expression. Histone deacetylases inhibitors such as valproic acid, vorinostat have attracted interest because of their ability to induce differentiation and apoptosis of cancer cells. The current study was designed to assess the effect of valproic acid in comparison to and in combination with vorinostat on cell growth inhibition and apoptosis induction in the human colon cancer SW48 cells. Materials and Methods: The colon cancer SW48 cells were seeded and treated with various doses of valproic acid and vorinostat and MTT assay and flow cytometric assay were done to determine cell viability and cell apoptosis, respectively. Results: All concentrations of both agents reduced viability significantly in a dose- and time-dependent fashion (p < 0.004). Both compounds, either single or combined agents, induced apoptosis significantly, whereas the ratio of the apoptotic cells treated with combined agents was more significant than the single. Conclusion: Our findings suggest that vaproic acid and vorinostat can significantly inhibit cell growth and induce apoptosis in colon cancer SW48 cells.
DETERMINATION OF OXYGEN PERFUSION IN THE AREA OF RADIATION-INDUCED FIBROSIS OF THE SKIN IN PATIENTS WITH BREAST CANCER AND ITS ROLE IN PATHOGENESIS OF LATE RADIATION INJURY
Authors: Agishev T T , Topuzov E E , Кrasnozhon D A , Petrachkov A O , Pavlov R V , Doniyarov S H
Published: January 2019

Aim: Late radiation injury in the form of radiation-induced fibrosis (RIF) is one of the many complications of radiation therapy. The aim was to evaluate oxygen perfusion in the skin in the area of late radiation injury manifested as RIF in patients with breast cancer. Materials and Methods: Based on our first-hand experience in treating late radiation injures of soft tissues in patients with breast cancer, we measured oxygen perfusion of the skin (tсрО2) in the area of late radiation injury using a transcutaneous monitor (oximeter) TCM 400 (Radiometer, Denmark). Results: Partial oxygen pressure tcpO2 in the RIF area in patients with breast cancer didn’t show any significant decrease compared to healthy tissue. Mean value of partial oxygen pressure tcpO2 in the RIF area was 42.650 ± 9.178 mmHg, in the healthy tissue it was 45.180 ± 8.025 mmHg. Maximal difference in tcpO2 between the damaged and healthy tissue was 30 mmHg. Conclusions: Results of the study suggest that there’s no significant difference between oxygen perfusion (tcpO2) in the area of RIF and healthy tissue.
ABO BLOOD GROUP AND THE RISK OF LUNG CANCER IN GREEK ADULTS: A CASE — CONTROL STUDY
Authors: Chrysanthakopoulos N A , Dareioti N S
Published: January 2019

Aim: The present study aimed to investigate any possible association between ABO blood groups and lung cancer. Materials and Methods: The study was conducted on 122 lung cancer patients and 1,255 matched-healthy individuals that were reviewed retrospectively. Chi-square and logistic regression models were used for statistical analysis. Results: No significant difference between lung cancer patients and the control group was recorded regarding ABO blood types and the risk of lung cancer (p = 0.055, OR = 0.79, 95% CI 0.61–1.03). Male gender (p = 0.006, OR = 2.08, 95% CI 1.24–3.49) and smoking (p = 0.000, OR = 3.13, 95% CI 1.72–5.69) were significantly associated with the risk of lung cancer. Conclusion: No association between ABO blood types and the risk of lung cancer was observed.
THE EFFECTS OF EARLY POSTOPERATIVE IMMUNIZATION WITH XENOGENEIC EMBRYO PROTEINS ON LEWIS LUNG CARCINOMA MODEL
Authors: Symchych T V , Fedosova N I , Karaman O M , Voeykova I M , Didenko G V
Published: January 2019

Aim: To investigate the effect of chicken embryo proteins (CEP) as a prototype of xenogeneic vaccine on immune reactions in mice immunized after Lewis lung carcinoma (LLC) surgical removal. Materials and Methods: C57Bl male mice were immunized on days 1, 8, and 15 after surgical removal of LLC. The immune response was assessed on days 7, 14, 21 and 28 after tumor resection. Cytotoxic activity of natural killer cells (NK) and cytotoxic T-lymphocytes as well as antibody dependent cellular cytotoxicity was estimated in MTT-assay; specific antibodies were detected in ELISA; lymphocyte proliferation was tested in reaction of in vitro blast transformation. Results: None of the immunized mice developed LLC metastases. Immunization with CEP seems to prevent the potential decrease in NK cell cytotoxic activity and spontaneous blast transformation activity of lymphocytes following the surgically induced stress. Further research on improving immunization schedule and elucidating the mechanisms of NK modulation with CEP is needed.
SERUM LEVEL OF DIPEPTIDYL PEPTIDASE-4 AS A POTENTIAL BIOMARKER FOR MEDULLARY THYROID CANCER
Authors: Abooshahab R , Niyazi E , Yaghmaie P , Ghadaksaz H G , Hedayati M
Published: January 2019

Aim: Adipokines are the proteins secreted from adipose tissue and play an important role in the control of metabolism. Dipeptidyl peptidase-4 (DPP4) is a novel adipokine with different biological role. As indicated by various studies, serum levels of DPP4 had been associated with body mass index (BMI), insulin resistance, metabolic syndrome and malignancy. The aim of this study was to assess the serum levels of DPP4 in patients with medullary thyroid cancer (MTC) in comparison with these in the control group. Materials and Methods: This study was performed on 45 MTC patients (24 females and 21 males) and 45 healthy controls (21 females and 24 males). DPP4 and insulin serum levels were measured by ELISA, fasting glucose serum levels by enzymecalorimetric method and insulin resistance index (HOMA-IR) by calculation using relevant equation. BMI (kg/m2) was also calculated. Results: Our data did not demonstrate a significant difference between serum DPP4 levels in MTC and healthy group (41.06 ± 22.08 ng/ml vs 39.94 ± 20.77 ng/ml, p > 0.05). Additionally, no significant difference was found in serum insulin and HOMA-IR concentrations between MTC patients and the controls (p > 0.05). Conclusions: This study suggests that the fluctuation in the levels of DPP4 does not play an important role in prognosis, early detection and diagnosis of MTC. Furthermore, higher levels of DPP4 cannot be considered as a risk factor for MTC.
CLINICAL SIGNIFICANCE OF SERUM CAVEOLIN-1 LEVELS IN GASTRIC CANCER PATIENTS
Authors: Tas F , Karabulut S , Erturk K , Duranyildiz D
Published: January 2019

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key
Perception of Benefits and Risks of Neurocognitive Disorders Diagnosis: A French National Survey
Authors: Garnier-Crussard Antoine , Vernaudon Julien , Auguste Nicolas , Moutet Claire , Dauphinot Virginie , Krolak-Salmon Pierre
Published: January 2019

Background:

Neurocognitive disorders (NCD) are underdiagnosed in primary care, mainly because of the misunderstanding of benefits associated with timely diagnosis.

Objective:

The aim of this study was to explore the benefits and risks of diagnosis in a population of general practitioners (GPs), specialized physicians (SPs), other healthcare professionals (HPs), and informal caregivers (ICs).

Methods:

A questionnaire was submitted to GPs, SPs, HPs. and ICs. It aimed at evaluating benefits and risks related to NCD diagnosis associated with four prototypical clinical cases at different stages: isolated cognitive complaint/mild NCD, major NCD at mild/moderate stage, moderate stage with behavioral and psychotic symptoms, and severe stage. The concepts of early, timely, and personalized diagnosis were evaluated.

Results:

A total of 719 completed surveys were collected from 183 GPs, 176 SPs, 281 HPs, and 79 ICs. More than 90% of the participants considered initiating a diagnosis as relevant except at the severe stage. Benefits were superior to risks for all groups and all four cases alike ( p < 0.001). Benefits were lower according to GPs and higher for SPs than the other groups at the first two stages ( p < 0.001). At the moderate stage, there were few differences between groups. At the severe stage, GPs and SPs claimed it was less relevant to carry out a diagnosis than the other groups ( p < 0.001). Risks were higher for ICs and lower for SPs ( p < 0.001). The best diagnosis concept was the personalized diagnosis.

Conclusion:

Benefits appeared more relevant than risks with differences according to the stage of the disease and type of respondents.
Neuroimaging Characteristics of Frailty Status in Patients with Alzheimer’s Disease
Authors: Hirose Daisuke , Shimizu Soichiro , Hirao Kentaro , Ogawa Yusuke , Sato Tomohiko , Kaneko Yoshitsugu , Takenoshita Naoto , Namioka Nayuta , Fukasawa Raita , Umahara Takahiko , Sakurai Hirofumi , Watanabe Ryo , Hanyu Haruo
Published: January 2019

Background/Objective:

Although frailty is closely linked to dementia, particularly Alzheimer’s disease (AD), underlying pathophysiology of frailty associated with AD remains uncertain. This study aimed to investigate differences in structural and functional brain imaging abnormalities between AD with and without frailty.

Methods:

A total of 191 outpatients with probable AD (men: 91; women: 100; age: 80.7±6.3 years) who underwent both magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) were enrolled in this study. Frailty was determined in accordance with the Obu study Health Promotion for the Elderly. We compared numbers of small infarctions in the subcortical gray and white matter and severity of white matter abnormalities (periventricular hyperintensity [PVH] and deep white matter hyperintensity [DWMH]) on MRI, and regional cerebral blood flow (rCBF) changes on SPECT between AD with and without frailty.

Results:

The prevalence of frailty was 43.4% in patients with AD. PVH and DWMH scores were significantly higher in AD with frailty compared to those without frailty. AD with frailty had a trend of decreased rCBF in the bilateral anterior cingulate gyrus, whereas those without frailty tend to have decreased rCBF in the left dominant parietal lobe and precuneus.

Conclusion:

Our MRI and SPECT imaging studies suggest different underlying pathophysiology in the brain between AD with frailty and without frailty.
Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits
Authors: Chen Yuanxin , Wang Tianduo , Rogers Kem A. , Rutt Brian K. , Ronald John A.
Published: January 2019

Microglial activation and oxidative stress have been linked to the formation of amyloid plaques found in Alzheimer’s disease (AD). Epidemiologic and experimental evidence also suggests that cholesterol (CH) contributes to the pathogenesis of AD, particularly the formation of amyloid plaques. We have previously described the development of amyloid-β (Aβ) plaques in New Zealand white rabbits maintained on a 0.125%–0.25% w/w CH diet for extended periods of time (28 months). Here we further characterize this model with combined immunofluorescence and immunohistochemical staining to evaluate markers of immune cell activation. Five out of eight CH-fed rabbits, but not control rabbits, developed extracellular Aβ plaques in both the hippocampus and cortex. Significantly ( p < 0.05) higher CD11b microglial staining was found in the hippocampus, temporal cortex, and frontal cortex of CH-fed versus control rabbits. In the temporal cortex and parietal cortex, active CD-11b- and ferritin-positive microglia were found in close proximity to Aβ plaques. Classification and quantification of activated microglia in the temporal cortex showed that 68±12.9%, 25±7.3%, and 7±2.7% of all microglia had a primed, reactive, and amoeboid phenotype, respectively. Activated microglia also expressed myeloperoxidase which was co-localized to amyloid deposits. Our findings in this dietary-based model lend further support of a role of activated microglia and oxidative stress during the development of AD and strengthens the links between hypercholesterolemia, inflammatory status, and AD.
Subjective Cognitive Impairment in 55-65-Year-Old Adults Is Associated with Negative Affective Symptoms, Neuroticism, and Poor Quality of Life
Authors: Jenkins Amy , Tree Jeremy J. , Thornton Ian M. , Tales Andrea
Published: January 2019

Although subjective cognitive impairment (SCI) is increasingly recognized clinically and in research as a risk factor for mild cognitive impairment and dementia (particularly Alzheimer’s disease), it is etiologically heterogeneous and potentially treatable. Compared to mild cognitive impairment and Alzheimer’s disease, SCI however remains poorly characterized with debate continuing regarding its clinical relevance. The primary aim of this study was to improve the characterization of SCI within the general public by investigating functions sometimes omitted clinically or in research, namely visual attention-related information processing speed (RT) and its intra-individual variability (IIVRT), general cognition, depression, anxiety, memory, quality of life (QOL), and neuroticism. Compared to individuals without SCI, those with SCI were more likely to reveal higher scores of anxiety, depression, and neuroticism and poorer perceived physical, psychological, and environmental QOL. Within-group analysis identified no significant relationships between any of the above variables for the non-SCI group whereas for the SCI group, poorer Cognitive Change Index scores were significantly correlated with slower RT, raised IIVRT, poorer memory, negative affective symptoms, higher neuroticism scores, and poorer QOL. This indicates that reports of perceived memory changes in SCI can also be associated with other characteristics, namely objectively measured detrimental change in other aspects of brain function and behavior. This outcome emphasizes the importance of a multi-function approach to characterizing and understanding SCI. Thus, although the effect of RT and IIVRT is not strong enough to differentiate SCI from non-SCI at group level, slowing and raised IIVRT do appear to characterize some people with SCI.
Immediate Intervention Effects of Standardized Multicomponent Group Interventions on People with Cognitive Impairment: A Systematic Review
Authors: Özbe Dominik , Graessel Elmar , Donath Carolin , Pendergrass Anna
Published: January 2019

Background:

There is no curative medical treatment for dementia. Therefore, researchers turned their attention to non-pharmacological treatment approaches. Many reviews analyzed the efficacy of single-component interventions, but there has been no systematic review of multicomponent interventions so far.

Objective:

The aim was to systematically review studies using standardized multicomponent group interventions for persons with dementia or persons with mild cognitive impairment (MCI) and to analyze their immediate intervention effects.

Methods:

The databases PubMed, PsycINFO, PSYNDEX, and CINAHL were systematically searched. We included randomized controlled trials with people with MCI or dementia, which implemented interventions with at least two components that targeted different outcome domains. Additionally, the intervention had to be standardized and in a group setting.

Results:

Nine studies met the inclusion criteria with a total sample size of N = 513 participants. Six studies applied two, two studies applied three, and one study applied four components. Four studies, which combined at least a physical and a cognitive component, had a positive effect on non-cognitive symptoms of dementia. Two of these interventions additionally had a positive effect on cognitive abilities. One study reported a positive effect on activities of daily living and another study showed an effect on quality of life.

Conclusion:

In spite of the heterogeneity of the studies, multicomponent interventions suggest a positive effect on non-cognitive symptoms, especially the combination of cognitive and physical components. Single studies had also an effect on additional outcome domains. By trend the effects are dependent on application rate and used assessments.
Influence of magnetic forces and magnetostriction on the vibration behavior of an induction motor
Authors: Sathyan Sabin , Aydin Ugur , Lehikoinen Antti , Belahcen Anouar , Vaimann Toomas , Kataja Juhani
Published: January 2019

This paper presents the vibration analysis and results of an induction motor through two kinds of magneto-mechanical coupling methods. The computation results are validated by comparing them with the vibration measurements of the motor. The role of both the magnetic forces and magnetostriction are examined and distinguished based on their contribution to the vibration behavior of the machine. It was found that the pole pair number of an induction machine can affect the way the vibrations caused by magnetostriction and magnetic forces either add up or oppose each other.
The racial ‘digital divide’ in the predictive power of Google trends data for forecasting the unemployment rate
Authors: Dilmaghani Maryam
Published: January 2019

The present paper mines time-series of job search queries from Google Trends to predict the unemployment rates of Americans between 16 and 24 years of age. The predictive power of Google Trends data is found to be notably higher in forecasting the unemployment rate of Whites compared with Hispanics, as well as African Americans for whom the fit is rather poor. Acknowledging the differences in the opportunity cost of time between the employed and the unemployed, the time-series related to inexpensive online leisure are also retrieved from Google Trends, and the prediction models are augmented by these variables. The analysis reveals that the inclusion of inexpensive online leisure queries in the models significantly improves the out-of-sample prediction for Hispanics. The implications of this study for the use of big data in forecasting unemployment rates are explored.